The remarkable global development of disease-modifying therapies （DMTs） specific for multiple sclerosis （MS） has significantly reduced the frequency of relapse, slowed the progression of disability, and improved t...The remarkable global development of disease-modifying therapies （DMTs） specific for multiple sclerosis （MS） has significantly reduced the frequency of relapse, slowed the progression of disability, and improved the quality of life in patients with MS. With increasing numbers of approved DMTs, neurologists in North America and Europe are able to present multiple treatment options to their patients to achieve a better therapeutic outcome, and in many cases, no evidence of disease activity. MS patients have improved accessibility to various DMTs at no or minimal out-of-pocket cost. The ethical guidelines defined by the Edinburgh revision of the Declaration of Helsinki strongly discourage the use of placebo control groups in modern MS clinical trials. The use of an active comparator control group increases the number of participants in each group that is essential to achieve statistical significance, thus further increasing the difficulty of completing randomized controlled trials （RCTs） for the development of new MS therapies. There is evidence of a high prevalence of MS and a large number of patients in Asia. The belief of the existence of Asian types of MS that are distinct from Western types, and regulatory policies are among the reasons why DMTs are limited in most Asian countries. Lack of access to approved DMTs provides a good opportunity for clinical trials that are designed for the development of new MS therapies. Recently, data from RCTs have demonstrated excellent recruitment of participants and the completion of multi-nation and single-nation MS trials within this region. Recent studies using the McDonald MS diagnostic criteria carefully excluded patients with neuromyelitis optica （NMO） and NMO spectrum disorder, and demonstrated that patients with MS in Asia have clinical characteristics and treatment responses similar to those in Western countries.展开更多
The approval of oral disease modifying therapies(DMTs) for relapsing-remitting multiple sclerosis(RRMS) has changed considerably the therapeutic scenario and they often represent the first therapeutic choice for patie...The approval of oral disease modifying therapies(DMTs) for relapsing-remitting multiple sclerosis(RRMS) has changed considerably the therapeutic scenario and they often represent the first therapeutic choice for patients with RRMS,since their safety and efficacy profile has been extensively validated(D'Amico et al.,2015).展开更多
Since disability in multiple sclerosis(MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug developm...Since disability in multiple sclerosis(MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug development. In particular, remyelination treatments could promote return of neurological function and also prevent further axonal loss and neurodegeneration in MS due to trophic effects of myelin. The study of remyelination has advanced dramatically in the last several years such that a number of pathways inhibiting remyelination have been discovered, including those involving LINGO-1, Notch-1, hyaluronan, retinoid X receptor, and wnt/?-catenin. Other approaches such as high throughput drug screening for remyelination drugs have caught fire, with identification of dozens of known drugs with oligodendrocyte maturation stimulatory effects. Several drugs identified through screens and other mechanisms are in the process of being further evaluated for remyelination in MS and MS models. We discuss the potential molecular targets and the variety of mechanisms towards drug identification and development in remyelination for MS.展开更多
Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord under...Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).展开更多
Objective To explore the effects of acupuncture in comparison with sham acupuncture on cognitive functions in patients with relapsing-remitting multiple sclerosis(RRMS).Methods In this randomized controlled trial,31 R...Objective To explore the effects of acupuncture in comparison with sham acupuncture on cognitive functions in patients with relapsing-remitting multiple sclerosis(RRMS).Methods In this randomized controlled trial,31 RRMS patients in the acupuncture group were treated with traditional Chinese acupuncture based on the treatment principle of calming the mind,reinforcing qi and blood,and 31 patients in the control group were treated with sham acupuncture(shallow needling at non-acupuncture points)twice a week for 12 weeks.The primary outcome was the Brief International Cognitive Assessment for Multiple Sclerosis(BICAMS)score,which was evaluated by a psychologist at baseline and after 12 weeks of treatment.The secondary outcomes were the Symptom Checklist 90-Revised(SCL-90-R),Pittsburgh Sleep Quality Index(PSQI),and Fatigue Severity Scale(FSS)scores.The participants were provided with contact information from the researchers with constant access to report any adverse symptoms.Results In total,62 participants were enrolled and allocated to the acupuncture group(31 cases)or control group(31 cases).After 12 weeks of acupuncture treatment,BICAMS including Symbol Digit Modalities Test(SDMT),California Verbal Learning Test-2(CVLT-2)and delayed CVLT-2 scores were significantly improved in comparison with the control group(P<0.01).However,the changes in the Brief Visuospatial Memory Test-Revised(BVMT-R)and delayed BVMT-R scores related to visual/spatial memory did not differ significantly between the two groups(both P>0.05).The FSS,PSQI,and SCL-90-R scores were significantly reduced after 12-week treatment in the acupuncture group compared to the control group(P<0.05 or P<0.01).No life-threatening adverse events occurred throughout the study.Conclusions Twelve weeks of acupuncture treatment was effective in improving immediate and short-term auditory/verbal memory,attention and processing speed;reducing fatigue and decreasing sleep latency and the use of sleeping medications;alleviating depression,somatization,obsessive-compulsive and paranoid disorders in patients with RRMS.展开更多
Neuromyelitis optica spectrum disorders, or neuromyelitis optica(NMO), is an autoimmune disease of the central nervous system that must be distinguished from multiple sclerosis. Therapeutic approaches to relapse preve...Neuromyelitis optica spectrum disorders, or neuromyelitis optica(NMO), is an autoimmune disease of the central nervous system that must be distinguished from multiple sclerosis. Therapeutic approaches to relapse prevention in NMO include immunosuppressants and monoclonal antibodies. Rituximab, a monoclonal antibody that targets CD20 antigen expressed on the surface of pre-B, mature B-lymphocytes and a small subset of T-lymphocytes, has been widely used for the treatment of NMO. In this review, we aim to summarize global experience with rituximab in NMO. We identified 13 observational studies that involved a total of 209 NMO patients treated with rituximab. Majority of rituximab-treated patients evidenced stabilization or improvements in their disability scores compared to pre-treatment period and 66% of patients remained relapse-free during treatment period. Monitoring rituximab treatment response with CD19+ or CD27+ cell counts appears to improve treatment outcomes. We offer clinical pointers on rituximab use for NMO based on the literature and authors' experience, and pose questions that would need to be addressed in future studies.展开更多
For many years,quantifiable biomarkers in neurological diseases have represented a hot topic.In multiple sclerosis(MS),cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's...For many years,quantifiable biomarkers in neurological diseases have represented a hot topic.In multiple sclerosis(MS),cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983,with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001.Nowadays,that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event,according to the 2017 revised McDonald criteria.Possibly kappa free light chains,N-CAM,chitinase 3-like protein 1 and IgM oligoclonal bands,not yet implemented in clinical practice,could similarly gain importance in the near future.Furthermore,the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity,better defining the MS phenotype and patients with highly active disease.Accordingly,myelin proteins,intermediate filaments,metalloproteinases and other molecules involved in the inflammatory cascade,are currently under investigation.Finally,it has long been known that axonal loss occurs from the early phases,leading to a progressive neurological deterioration.Since established criteria to assess treatment failure and transition to progressive forms are still lacking,both treatment response and prognostic biomarkers would be useful to predict MS course,and neurofilaments seem to have this potential.The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.展开更多
Background: Intravenous immunoglobulin (IVIg) has been reported to reduce dise ase activity in patients with relapsingremitting multiple sclerosis. We assessed the effect of IVIg treatment in patients after the first ...Background: Intravenous immunoglobulin (IVIg) has been reported to reduce dise ase activity in patients with relapsingremitting multiple sclerosis. We assessed the effect of IVIg treatment in patients after the first neurological event sug gestive of demyelinative disease and evaluated the occurrence of a second attack and dissemination in time demonstrated by brain magnetic resonance imaging with in the first year from onset. Methods: We conducted a randomized, placebo con trolled, double blind study in 91 eligible patients enrolled within the first 6 weeks of neurological symptoms. Patients were randomly assigned to receive IVIg treatment (2 g/kg loading dose) or placebo, with boosters (0.4 g/kg) given onc e every 6 weeks for 1 year. Neurological and clinical assessments were done ever y 3 months, and brain magnetic resonance imaging was performed at baseline and t he end of the study. Results: The cumulative probability of developing clinicall y definite multiple sclerosis was significantly lower in the IVIg treatment grou p compared with the placebo group (rate ratio, 0.36 [95%confidence interval, 0 . 15 0.88]; P = .03). Patients in the IVIg treatment group had a significant red u ction in the volume and number of T2 weighted lesions and in the volume of gado lin ium enhancing lesions as compared with the placebo group (P = .01, P = .01 , and P = .03, respectively). Treatment was well tolerated, compliance was high, and incidence of adverse effects did not differ significantly between groups. C onclusions: Intravenous immunoglobulin treatment for the first year from onset o f the first neurological event suggestive of demyelinative disease significantly lowers the incidence of a second attack and reduces disease activity as measure d by brain magnetic resonance imaging.展开更多
Background and objective: Multiple sclerosis (MS) is a chronic, progressive di sease of the central nervous system that generally occurs in adults under the ag e of 40 years and ultimately leads to severe neurological...Background and objective: Multiple sclerosis (MS) is a chronic, progressive di sease of the central nervous system that generally occurs in adults under the ag e of 40 years and ultimately leads to severe neurological disability. Following the progression of MS by monitoring changes in disability levels can facilitate treatment decisions taken by physicians. The aim of this review is to present lo ngitudinal disability curves enabling the assessment of disease progression in p atients with relapsingremitting (RR)MS. Methods: Patients with a definite diagno sis of MS and an RR disease course were identified using the Multiple Sclerosis Center computerised database. Patients were stratified into major percentile gro ups based on their Expanded Disability Status Scale (EDSS) score 1 year after di sease onset. Model disability curves for each percentile were constructed using mean consecutive EDSS scores for 10 years after disease onset. Model curves were generated by smoothing (parametric and non parametric regression) and curve ap proximation (lin ear regression and moving averages). The predictive ability of model curves was validated by superimposing data from a separate group of patie nts with RRMS. Results: Disability curves were constructed using data from 1001 patients. A significant difference between the initial percentile assignment and disability progression was indicated by the log rank test (p <0.001). Kaplan Meier and life table analyses demonstrated the validity of the model in predicti ng disease progression. The probability of experiencing more severe disability t han predicted (i. e. deviating from the initial percentile to a higher percentil e over time) ranged from 6.5%(50 th percentile) to 15.4%(75th percentile), whi le the probability of experiencing less severe disability than predicted (i. e. deviating from the initially assigned percentile to a lower percentile over time ) ranged from 6.9%(50th percentile) to 1.6%(75th percentile). Both suggest rea sonable predictive validity. Conclusion: In MS, longitudinal disability curves c an help to assess individual patient disability, map the effects of immunomodula tory treatments over time, and generally build on the overall clinical impressio n of disease progression. Such models can act as a tool to aid and support the c linical decision making process. This review is based on the study published in Multiple Sclerosis (2003) 9:486-491.展开更多
Acute exacerbations may complicate the course of pregnancy and the postpartum period in patients with relapsing- remitting multiple sclerosis (RRMS). To evaluate relapse rate and the effect of immunomodulatory treatme...Acute exacerbations may complicate the course of pregnancy and the postpartum period in patients with relapsing- remitting multiple sclerosis (RRMS). To evaluate relapse rate and the effect of immunomodulatory treatment with intravenous immunoglobulin (IVIg) during pregnancy and the postpartum period we retrospectively analysed the data of 108 pregnant RRMS patients. Group I patients were not treated, Group II patients were treated with IVIg 0.4 g/kg body weight/day for 5 consecutive days within the first week after delivery with additional booster doses of 0.4 g/kg body weight/day at 6 and 12 weeks postpartum (defined as 12 weeks after labor), and Group III patients were treated continuously with IVIg during gestation and the postpartum period (0.4 g/kg body weight/day for 5 consecutive days within the 6- 8 weeks of gestation with additional booster doses of 0.4 g/kg body weight/day once every 6 weeks until 12 weeks postpartum). All patients underwent antenatal care and fetal ultrasonographic surveillance examinations. Relapse rate per woman per year during the pregnancy and the postpartum period as well as neonatal outcome data and IVIg related adverse events were analysed. Relapse rate per woman per year for patients treated with IVIg for the whole pregnancy and postpartum period (Group III, N = 28) compared with the untreated Group I patients (N = 39) were as follows: first trimester 0.43 vs. 0.72, second trimester 0.15 vs. 0.61, third trimester 0.0 vs. 0.41, and postpartum period 0.28 vs.1.33 (p< 0.05). Patients treated with IVIg only during the postpartum period (Group Ⅱ , N = 41) also showed a decrease in relapse rate compared with untreated Group I patients, 0.58 vs. 1.33 (p = 0.012). The mean maternal age, disease duration, gestational age at delivery and fetal delivery weight did not significantly differ between the three groups. Mode of delivery, obstetrical complications, the use of epidural analgesia and breast- feeding, did not affect postpartum relapse rate. No severe adverse events were associated with IVIg treatment either during the pregnancy or postpartum period for the patients and newborns. We conclude that in RRMS patients IVIg treatment could be considered as an optional treatment to reduce the incidence of pregnancy and postpartum- related relapses. Further randomized double- blind studies are needed to confirm our findings.展开更多
Background: African Americans (AAs) with multiple sclerosis (MS) seem to have a more severe disease course than white Americans (WAs). To our knowledge, it is not known to what extent treatment with interferon beta-1a...Background: African Americans (AAs) with multiple sclerosis (MS) seem to have a more severe disease course than white Americans (WAs). To our knowledge, it is not known to what extent treatment with interferon beta-1a will effect the MS disease course within the AA population. Objective: To compare the response to treatment with interferon beta-1a between AA and WA MS patients. Design: This is an exploratory post hoc analysis of the Evidence of Interferon Dose-Response: European North American Comparative Efficacy (EVIDENCE) study. Setting: The EVID ENCE study is a randomized controlled trial that compared the efficacy of once weekly, intramuscular, 30-μg interferon beta-1a treatment with thrice weekly, subcutaneous, 44-μg interferon beta-1a therapy in treatment-nave MS subjects. Participants: Thirty-six AA subjects were compared with 616 WA subjects. Main Outcome Measures: The number of MS exacerbatio ns, the proportion of exacerbation-free subjects, and the number of new MS lesions present on brain magnetic resonance imaging were compared between AA and WA subjects at 24 and 48 weeks after initiating treatment with interferon beta-1a. Results: The AA subjects experienced more exacerbations and were less likely to remain exacerbation free (statistical trends). The AA subjects developed more new MS lesions on T2-weighted brain magnetic resonance imaging at 48 weeks (P=.04). Conclusions: Despite the small sample size, AA subjects appeared less responsive to treatment than WA subj ects on outcome measures, reaching significance only for T2-weighted lesion count at 48 weeks. However, it is difficult to base these differences solely on response to treatment given the potential differing in MS disease course in AA patients.展开更多
Objective: To explore the potential of dexrazoxane to suppress subclinical cardiotoxicity in MS patients receiving mitoxantrone. Methods: An open-label study was performed to evaluate possible subclinical cardiotoxici...Objective: To explore the potential of dexrazoxane to suppress subclinical cardiotoxicity in MS patients receiving mitoxantrone. Methods: An open-label study was performed to evaluate possible subclinical cardiotoxicity in multiple sclerosis patients treated quarterly with mitoxantrone (48mg/m2 cumulative), with and without concomitant dexrazoxane, using blinded serial radionucleide ventriculography. Results: No patient experienced symptoms of heart failure. Patients receiving dexrazoxane, which is cardioprotective for anthracyclines, exhibited a significantly lesser decline in left ventricular ejection fraction (mean change, - 3.80% vs - 8.55% , p < 0.001). Interpretation: These results support a cardioprotective effect of dexrazoxane in mitoxantrone treated multiple sclerosis patients.展开更多
Main text The disruption of protein folding homeostasis in motoneurons(MNs)and the accumulation of protein aggregates are some of the main molecular hallmarks of amyotrophic lateral sclerosis(ALS).Evidence from sporad...Main text The disruption of protein folding homeostasis in motoneurons(MNs)and the accumulation of protein aggregates are some of the main molecular hallmarks of amyotrophic lateral sclerosis(ALS).Evidence from sporadic and familial ALS(fALS)patients and from ALS models suggests that protein aggregation directly participates in neurodegeneration.In turn,the loss of MN homeostasis triggers a coping mechanism,the integrated stress response(ISR)[1].The ISR is initiated by four independent stress-sensing kinases,each of them activated by distinct stresses:protein kinase R(PKR)by double-strand RNA,protein kinase RNA-like endoplasmic reticulum kinase(PERK)by protein misfolding at the endoplasmic reticulum(ER),general control nonderepressible 2(GCN2)by nutrient starvation,and heme-regulated inhibitor(HRI)by heme deprivation.展开更多
Background Our previous study had demonstrated that ulinastatin （UTI） had a neuroprotective effect in experimental autoimmune encephalomyelitis （EAE）. Methylprednisolone has been recommended to be a standard drug ...Background Our previous study had demonstrated that ulinastatin （UTI） had a neuroprotective effect in experimental autoimmune encephalomyelitis （EAE）. Methylprednisolone has been recommended to be a standard drug in multiple sclerosis （MS） therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE. Methods Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2＇,3＇-cyclic nucleotide 3＇- phosphodiesterase （CNP）/myelin basic protein （MBP）/the precursor form of nerve growth factor （proNGF）/p75/inducible nitric oxide synthase （iNOS） proteins in cerebral cortex of EAE were detected by Western blotting. Results The combined treatment group had a lower clinical score （0.61±0.06） and demyelinating score （1.33±0.33） than the groups with normal saline （clinical score： 1.39±0.08, P 〈0.001; demyelinating score： 2.75±0.49, P 〈0.05） or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP （1.14±0.06 vs. 0.65±0.04, P 〈0.001）, MBP （1.28±0.14 vs. 0.44±0.17, P 〈0.001）, and decreased expressions of proNGF （1.08±0.10 vs. 2.32±0.12, P 〈0.001）, p75 （1.13±0.13 vs. 2.33±0.17, P 〈0.001）, and iNOS （1.05±0.31 vs. 2.17±0.13, P 〈0.001） proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP （1.28±0.14 vs. 1.01±0.15, P 〈0.05） expression and downregulate iNOS （1.05±0.31 vs. 1.35±0.14, P 〈0.05） expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment （1.08±0.10） than that in UTI （1.51±0.24, P 〈0.05） or methylprednisolone （1.31±0.04, P 〈0.05） treatment group. Conclusion Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.展开更多
Background Bilirubin is the end product of heme catabolism and has strong antioxidant properties. Serum bilirubin levels are reported to be reduced in patients with multiple sclerosis （MS） and neuromyelitis optica ...Background Bilirubin is the end product of heme catabolism and has strong antioxidant properties. Serum bilirubin levels are reported to be reduced in patients with multiple sclerosis （MS） and neuromyelitis optica （NMO）. The pathophysiology of optic neuritis （ON） resembles that of MS; however, the role of endogenous bilirubin in ON is unclear. The aim of this study is to measure serum bilirubin levels in patients with ON, and to investigate the correlation between ON and serum antioxidant status of bilirubin. Methods Serum levels of bilirubin were measured in 42 patients with ON, 50 patients with multiple sclerosis （MS）, 48 patients with neuromyelitis optica （NMO） and 48 healthy control subjects. Results Serum total bilirubin （Tbil）, direct bilirubin （Dbil） and indirect bilirubin （Ibil） levels in patients with ON were significantly lower than those in the healthy controls. However, no statistical significance was found between levels in the ON and MS, ON and NMO, and MS and NMO groups. In patients with ON, serum Tbil, Dbil, and Ibil levels were lower in those with recurrence or those with ON for a longer duration （〉1 year）. Moreover, Tbil, Dbil, and Ibil concentrations were lower in patients with papillitis than in those with retrobulbar type ON, but the differences were not statistically significant. Conclusions Low antioxidant status may exist in patients with ON. But serum levels of Tbil, Dbil, and Ibil did not correlate with clinical presentations, such as recurrence, duration of disease and subtypes of ON. Low antioxidant status already existed in MS or NMO patients before systemic symptoms appeared.展开更多
Voltage-gated potassium channels(VGKCs)represent a group of tetrameric signaling proteins with several functions,including modulation of neuronal excitability and neurotransmitter release.Moreover,VGKCs give a key con...Voltage-gated potassium channels(VGKCs)represent a group of tetrameric signaling proteins with several functions,including modulation of neuronal excitability and neurotransmitter release.Moreover,VGKCs give a key contribution to the generation of the action potential.VGKCs are complexed with other neuronal proteins,and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients.By contrast,these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts.These three proteins are contactin-associated protein-2(Caspr-2),leucine-rich,glioma inactivated 1(LGI-1)protein and the protein Tag-1/contactin-2.Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1.Among all the cancers described in association with VGKC complex-IgG,lung carcinoma,thymoma,and hematologic malignancies are the most commonly detected.We will review all the major neurological conditions associated with VGKC complex-IgG.These include Isaacs’syndrome,Morvan syndrome,limbic encephalitis,facio-brachial dystonic seizures,chorea and other movement disorders,epilepsy,psychosis,gastrointestinal neuromuscular diseases,a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain.The vast majority of these conditions are reversible by immunotherapy,and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment.As a result,VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy,memory or cognitive problems,or peripheral nerve hyperexcitability syndromes.展开更多
In recent years,anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis overlapping with demyelinating disorders has attracted more and more attention.The case is about a 52-year-old woman with anti-NMDAR encephalitis p...In recent years,anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis overlapping with demyelinating disorders has attracted more and more attention.The case is about a 52-year-old woman with anti-NMDAR encephalitis presenting acute disseminated encephalomyelitis(ADEM)-like clinical/magnetic resonance(MR)findings.Here,the authors report this case and briefly review her MR evolution and the conditions of her prognosis.The recognition that patients with anti-NMDAR encephalitis may have demyelinating disorders,simultaneously or sequentially,is important.Otherwise,a high dose of steroid treatment with several courses could obtain good effect,even if given in the late phase.展开更多
Objective To compare the clinical characteristics of CTD-LETM-NMOSD patients to CTD-LETM-non-NMOSD patients.Methods We retrospectively collected data from 40 CTD patients with LETM who were admitted to the Department ...Objective To compare the clinical characteristics of CTD-LETM-NMOSD patients to CTD-LETM-non-NMOSD patients.Methods We retrospectively collected data from 40 CTD patients with LETM who were admitted to the Department of Neurology or Rheumatology at Peking Union Medical College Hospital from Jan,2006 to Dec,2016.展开更多
Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1...Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human intestines.While CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to adults.These findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to blood.Co-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells.Taken together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.展开更多
文摘The remarkable global development of disease-modifying therapies （DMTs） specific for multiple sclerosis （MS） has significantly reduced the frequency of relapse, slowed the progression of disability, and improved the quality of life in patients with MS. With increasing numbers of approved DMTs, neurologists in North America and Europe are able to present multiple treatment options to their patients to achieve a better therapeutic outcome, and in many cases, no evidence of disease activity. MS patients have improved accessibility to various DMTs at no or minimal out-of-pocket cost. The ethical guidelines defined by the Edinburgh revision of the Declaration of Helsinki strongly discourage the use of placebo control groups in modern MS clinical trials. The use of an active comparator control group increases the number of participants in each group that is essential to achieve statistical significance, thus further increasing the difficulty of completing randomized controlled trials （RCTs） for the development of new MS therapies. There is evidence of a high prevalence of MS and a large number of patients in Asia. The belief of the existence of Asian types of MS that are distinct from Western types, and regulatory policies are among the reasons why DMTs are limited in most Asian countries. Lack of access to approved DMTs provides a good opportunity for clinical trials that are designed for the development of new MS therapies. Recently, data from RCTs have demonstrated excellent recruitment of participants and the completion of multi-nation and single-nation MS trials within this region. Recent studies using the McDonald MS diagnostic criteria carefully excluded patients with neuromyelitis optica （NMO） and NMO spectrum disorder, and demonstrated that patients with MS in Asia have clinical characteristics and treatment responses similar to those in Western countries.
文摘The approval of oral disease modifying therapies(DMTs) for relapsing-remitting multiple sclerosis(RRMS) has changed considerably the therapeutic scenario and they often represent the first therapeutic choice for patients with RRMS,since their safety and efficacy profile has been extensively validated(D'Amico et al.,2015).
文摘Since disability in multiple sclerosis(MS) is a product of neurodegeneration and deficient remyelination, the ability to enhance neuroregeneration and myelin regeneration in MS is an enticing goal for MS drug development. In particular, remyelination treatments could promote return of neurological function and also prevent further axonal loss and neurodegeneration in MS due to trophic effects of myelin. The study of remyelination has advanced dramatically in the last several years such that a number of pathways inhibiting remyelination have been discovered, including those involving LINGO-1, Notch-1, hyaluronan, retinoid X receptor, and wnt/?-catenin. Other approaches such as high throughput drug screening for remyelination drugs have caught fire, with identification of dozens of known drugs with oligodendrocyte maturation stimulatory effects. Several drugs identified through screens and other mechanisms are in the process of being further evaluated for remyelination in MS and MS models. We discuss the potential molecular targets and the variety of mechanisms towards drug identification and development in remyelination for MS.
基金funding support from the Canadian Institutes of Health Researchsupported by a Doctoral Studentship from the Wings for Life Foundation。
文摘Extensive neurodegeneration is a hallmark of traumatic spinal cord injury (SCI) that underlies permanent sensorimotor and autonomic impairments (Alizadeh et al.,2019).Following the primary impact,the spinal cord undergoes a cascade of secondary injury mechanisms that are driven by disruption of the blood-spinal cord ba rrier,vascula r inju ry,glial reactivity,neu roinfla mmation,oxidative stress,lipid peroxidation,and glutamate excitotoxicity that culminate in neuronal and oligodendroglial cell death,demyelination,and axonal damage(Alizadeh et al.,2019).To achieve a meaningful functional recovery after SCI,regeneration of new neurons and oligodendrocytes and their successful growth and integration within the neural network are critical steps for reconstructing the damaged spinal cord tissue (Fischer et al.,2020).
文摘Objective To explore the effects of acupuncture in comparison with sham acupuncture on cognitive functions in patients with relapsing-remitting multiple sclerosis(RRMS).Methods In this randomized controlled trial,31 RRMS patients in the acupuncture group were treated with traditional Chinese acupuncture based on the treatment principle of calming the mind,reinforcing qi and blood,and 31 patients in the control group were treated with sham acupuncture(shallow needling at non-acupuncture points)twice a week for 12 weeks.The primary outcome was the Brief International Cognitive Assessment for Multiple Sclerosis(BICAMS)score,which was evaluated by a psychologist at baseline and after 12 weeks of treatment.The secondary outcomes were the Symptom Checklist 90-Revised(SCL-90-R),Pittsburgh Sleep Quality Index(PSQI),and Fatigue Severity Scale(FSS)scores.The participants were provided with contact information from the researchers with constant access to report any adverse symptoms.Results In total,62 participants were enrolled and allocated to the acupuncture group(31 cases)or control group(31 cases).After 12 weeks of acupuncture treatment,BICAMS including Symbol Digit Modalities Test(SDMT),California Verbal Learning Test-2(CVLT-2)and delayed CVLT-2 scores were significantly improved in comparison with the control group(P<0.01).However,the changes in the Brief Visuospatial Memory Test-Revised(BVMT-R)and delayed BVMT-R scores related to visual/spatial memory did not differ significantly between the two groups(both P>0.05).The FSS,PSQI,and SCL-90-R scores were significantly reduced after 12-week treatment in the acupuncture group compared to the control group(P<0.05 or P<0.01).No life-threatening adverse events occurred throughout the study.Conclusions Twelve weeks of acupuncture treatment was effective in improving immediate and short-term auditory/verbal memory,attention and processing speed;reducing fatigue and decreasing sleep latency and the use of sleeping medications;alleviating depression,somatization,obsessive-compulsive and paranoid disorders in patients with RRMS.
基金Supported by The National Multiple Sclerosis Society(NMSS),Guthy-Jackson Charitable Foundation,EMD-Serono/Pfizer,Biogen Idec,Serono and Novartis,and served on advisory board for Biogen Idec(Kister I)
文摘Neuromyelitis optica spectrum disorders, or neuromyelitis optica(NMO), is an autoimmune disease of the central nervous system that must be distinguished from multiple sclerosis. Therapeutic approaches to relapse prevention in NMO include immunosuppressants and monoclonal antibodies. Rituximab, a monoclonal antibody that targets CD20 antigen expressed on the surface of pre-B, mature B-lymphocytes and a small subset of T-lymphocytes, has been widely used for the treatment of NMO. In this review, we aim to summarize global experience with rituximab in NMO. We identified 13 observational studies that involved a total of 209 NMO patients treated with rituximab. Majority of rituximab-treated patients evidenced stabilization or improvements in their disability scores compared to pre-treatment period and 66% of patients remained relapse-free during treatment period. Monitoring rituximab treatment response with CD19+ or CD27+ cell counts appears to improve treatment outcomes. We offer clinical pointers on rituximab use for NMO based on the literature and authors' experience, and pose questions that would need to be addressed in future studies.
文摘For many years,quantifiable biomarkers in neurological diseases have represented a hot topic.In multiple sclerosis(MS),cerebrospinal fluid biomarkers have played a diagnostic role since the introduction of Poser's criteria in 1983,with IgG oligoclonal bands playing a supporting role in an epoch prior to magnetic resonance imaging and a complementary one after the introduction of McDonald criteria in 2001.Nowadays,that supporting role has turned into a main one in substituting for dissemination in time and defining the diagnosis of MS in patients with a first clinical event,according to the 2017 revised McDonald criteria.Possibly kappa free light chains,N-CAM,chitinase 3-like protein 1 and IgM oligoclonal bands,not yet implemented in clinical practice,could similarly gain importance in the near future.Furthermore,the increasing knowledge of molecular mechanisms leading to chronic inflammation has enhanced interest in looking for biomarkers of disease activity,better defining the MS phenotype and patients with highly active disease.Accordingly,myelin proteins,intermediate filaments,metalloproteinases and other molecules involved in the inflammatory cascade,are currently under investigation.Finally,it has long been known that axonal loss occurs from the early phases,leading to a progressive neurological deterioration.Since established criteria to assess treatment failure and transition to progressive forms are still lacking,both treatment response and prognostic biomarkers would be useful to predict MS course,and neurofilaments seem to have this potential.The purpose of this review article was to illustrate biomarkers that have been already validated or require further validation after proving to be useful in exploratory studies and potentially could prove useful in clinical practice in the coming years.
文摘Background: Intravenous immunoglobulin (IVIg) has been reported to reduce dise ase activity in patients with relapsingremitting multiple sclerosis. We assessed the effect of IVIg treatment in patients after the first neurological event sug gestive of demyelinative disease and evaluated the occurrence of a second attack and dissemination in time demonstrated by brain magnetic resonance imaging with in the first year from onset. Methods: We conducted a randomized, placebo con trolled, double blind study in 91 eligible patients enrolled within the first 6 weeks of neurological symptoms. Patients were randomly assigned to receive IVIg treatment (2 g/kg loading dose) or placebo, with boosters (0.4 g/kg) given onc e every 6 weeks for 1 year. Neurological and clinical assessments were done ever y 3 months, and brain magnetic resonance imaging was performed at baseline and t he end of the study. Results: The cumulative probability of developing clinicall y definite multiple sclerosis was significantly lower in the IVIg treatment grou p compared with the placebo group (rate ratio, 0.36 [95%confidence interval, 0 . 15 0.88]; P = .03). Patients in the IVIg treatment group had a significant red u ction in the volume and number of T2 weighted lesions and in the volume of gado lin ium enhancing lesions as compared with the placebo group (P = .01, P = .01 , and P = .03, respectively). Treatment was well tolerated, compliance was high, and incidence of adverse effects did not differ significantly between groups. C onclusions: Intravenous immunoglobulin treatment for the first year from onset o f the first neurological event suggestive of demyelinative disease significantly lowers the incidence of a second attack and reduces disease activity as measure d by brain magnetic resonance imaging.
文摘Background and objective: Multiple sclerosis (MS) is a chronic, progressive di sease of the central nervous system that generally occurs in adults under the ag e of 40 years and ultimately leads to severe neurological disability. Following the progression of MS by monitoring changes in disability levels can facilitate treatment decisions taken by physicians. The aim of this review is to present lo ngitudinal disability curves enabling the assessment of disease progression in p atients with relapsingremitting (RR)MS. Methods: Patients with a definite diagno sis of MS and an RR disease course were identified using the Multiple Sclerosis Center computerised database. Patients were stratified into major percentile gro ups based on their Expanded Disability Status Scale (EDSS) score 1 year after di sease onset. Model disability curves for each percentile were constructed using mean consecutive EDSS scores for 10 years after disease onset. Model curves were generated by smoothing (parametric and non parametric regression) and curve ap proximation (lin ear regression and moving averages). The predictive ability of model curves was validated by superimposing data from a separate group of patie nts with RRMS. Results: Disability curves were constructed using data from 1001 patients. A significant difference between the initial percentile assignment and disability progression was indicated by the log rank test (p <0.001). Kaplan Meier and life table analyses demonstrated the validity of the model in predicti ng disease progression. The probability of experiencing more severe disability t han predicted (i. e. deviating from the initial percentile to a higher percentil e over time) ranged from 6.5%(50 th percentile) to 15.4%(75th percentile), whi le the probability of experiencing less severe disability than predicted (i. e. deviating from the initially assigned percentile to a lower percentile over time ) ranged from 6.9%(50th percentile) to 1.6%(75th percentile). Both suggest rea sonable predictive validity. Conclusion: In MS, longitudinal disability curves c an help to assess individual patient disability, map the effects of immunomodula tory treatments over time, and generally build on the overall clinical impressio n of disease progression. Such models can act as a tool to aid and support the c linical decision making process. This review is based on the study published in Multiple Sclerosis (2003) 9:486-491.
文摘Acute exacerbations may complicate the course of pregnancy and the postpartum period in patients with relapsing- remitting multiple sclerosis (RRMS). To evaluate relapse rate and the effect of immunomodulatory treatment with intravenous immunoglobulin (IVIg) during pregnancy and the postpartum period we retrospectively analysed the data of 108 pregnant RRMS patients. Group I patients were not treated, Group II patients were treated with IVIg 0.4 g/kg body weight/day for 5 consecutive days within the first week after delivery with additional booster doses of 0.4 g/kg body weight/day at 6 and 12 weeks postpartum (defined as 12 weeks after labor), and Group III patients were treated continuously with IVIg during gestation and the postpartum period (0.4 g/kg body weight/day for 5 consecutive days within the 6- 8 weeks of gestation with additional booster doses of 0.4 g/kg body weight/day once every 6 weeks until 12 weeks postpartum). All patients underwent antenatal care and fetal ultrasonographic surveillance examinations. Relapse rate per woman per year during the pregnancy and the postpartum period as well as neonatal outcome data and IVIg related adverse events were analysed. Relapse rate per woman per year for patients treated with IVIg for the whole pregnancy and postpartum period (Group III, N = 28) compared with the untreated Group I patients (N = 39) were as follows: first trimester 0.43 vs. 0.72, second trimester 0.15 vs. 0.61, third trimester 0.0 vs. 0.41, and postpartum period 0.28 vs.1.33 (p< 0.05). Patients treated with IVIg only during the postpartum period (Group Ⅱ , N = 41) also showed a decrease in relapse rate compared with untreated Group I patients, 0.58 vs. 1.33 (p = 0.012). The mean maternal age, disease duration, gestational age at delivery and fetal delivery weight did not significantly differ between the three groups. Mode of delivery, obstetrical complications, the use of epidural analgesia and breast- feeding, did not affect postpartum relapse rate. No severe adverse events were associated with IVIg treatment either during the pregnancy or postpartum period for the patients and newborns. We conclude that in RRMS patients IVIg treatment could be considered as an optional treatment to reduce the incidence of pregnancy and postpartum- related relapses. Further randomized double- blind studies are needed to confirm our findings.
文摘Background: African Americans (AAs) with multiple sclerosis (MS) seem to have a more severe disease course than white Americans (WAs). To our knowledge, it is not known to what extent treatment with interferon beta-1a will effect the MS disease course within the AA population. Objective: To compare the response to treatment with interferon beta-1a between AA and WA MS patients. Design: This is an exploratory post hoc analysis of the Evidence of Interferon Dose-Response: European North American Comparative Efficacy (EVIDENCE) study. Setting: The EVID ENCE study is a randomized controlled trial that compared the efficacy of once weekly, intramuscular, 30-μg interferon beta-1a treatment with thrice weekly, subcutaneous, 44-μg interferon beta-1a therapy in treatment-nave MS subjects. Participants: Thirty-six AA subjects were compared with 616 WA subjects. Main Outcome Measures: The number of MS exacerbatio ns, the proportion of exacerbation-free subjects, and the number of new MS lesions present on brain magnetic resonance imaging were compared between AA and WA subjects at 24 and 48 weeks after initiating treatment with interferon beta-1a. Results: The AA subjects experienced more exacerbations and were less likely to remain exacerbation free (statistical trends). The AA subjects developed more new MS lesions on T2-weighted brain magnetic resonance imaging at 48 weeks (P=.04). Conclusions: Despite the small sample size, AA subjects appeared less responsive to treatment than WA subj ects on outcome measures, reaching significance only for T2-weighted lesion count at 48 weeks. However, it is difficult to base these differences solely on response to treatment given the potential differing in MS disease course in AA patients.
文摘Objective: To explore the potential of dexrazoxane to suppress subclinical cardiotoxicity in MS patients receiving mitoxantrone. Methods: An open-label study was performed to evaluate possible subclinical cardiotoxicity in multiple sclerosis patients treated quarterly with mitoxantrone (48mg/m2 cumulative), with and without concomitant dexrazoxane, using blinded serial radionucleide ventriculography. Results: No patient experienced symptoms of heart failure. Patients receiving dexrazoxane, which is cardioprotective for anthracyclines, exhibited a significantly lesser decline in left ventricular ejection fraction (mean change, - 3.80% vs - 8.55% , p < 0.001). Interpretation: These results support a cardioprotective effect of dexrazoxane in mitoxantrone treated multiple sclerosis patients.
基金supported by PID2020-120497RB-I00 MCIU/AEI/https://doi.org/10.13039/501100011033,BFU2017-90043-P MCINN/AEI/https://doi.org/10.13039/501100011033/by FEDER“Una manera de hacer Europa”(MA and TA),Proyecto Intramural IdisNa 2022(MA),Fundación para la Investigación Médica Aplicada(FIMA)Proyectos I+D,2017(TA)and Fundación Occident and DalecandELA Association(MA)supported by República de Panamá,Programa de Becas IFARHU-SENACYT(reference number 270-2018-922),NP by AC FIMA pre-doctoral fellowship.
文摘Main text The disruption of protein folding homeostasis in motoneurons(MNs)and the accumulation of protein aggregates are some of the main molecular hallmarks of amyotrophic lateral sclerosis(ALS).Evidence from sporadic and familial ALS(fALS)patients and from ALS models suggests that protein aggregation directly participates in neurodegeneration.In turn,the loss of MN homeostasis triggers a coping mechanism,the integrated stress response(ISR)[1].The ISR is initiated by four independent stress-sensing kinases,each of them activated by distinct stresses:protein kinase R(PKR)by double-strand RNA,protein kinase RNA-like endoplasmic reticulum kinase(PERK)by protein misfolding at the endoplasmic reticulum(ER),general control nonderepressible 2(GCN2)by nutrient starvation,and heme-regulated inhibitor(HRI)by heme deprivation.
基金This research was supported by grants from the National Natural Science Foundation of China （No. 81171126） and Medical Research Foundation of Guangdong Province （No. B2013124）.
文摘Background Our previous study had demonstrated that ulinastatin （UTI） had a neuroprotective effect in experimental autoimmune encephalomyelitis （EAE）. Methylprednisolone has been recommended to be a standard drug in multiple sclerosis （MS） therapies. The present study was to investigate the protective effects of UTI combined methylprednisolone in EAE. Methods Mice were divided into a UTI treatment group, a methylprednisolone treatment group, a combined treatment group with UTI and methylprednisolone, a normal saline treatment group, and a normal control group. EAE mice were induced in groups receiving different combined treatments, or respective monotherapies. Demyelination was evaluated by Solochrome cyanin staining. 2＇,3＇-cyclic nucleotide 3＇- phosphodiesterase （CNP）/myelin basic protein （MBP）/the precursor form of nerve growth factor （proNGF）/p75/inducible nitric oxide synthase （iNOS） proteins in cerebral cortex of EAE were detected by Western blotting. Results The combined treatment group had a lower clinical score （0.61±0.06） and demyelinating score （1.33±0.33） than the groups with normal saline （clinical score： 1.39±0.08, P 〈0.001; demyelinating score： 2.75±0.49, P 〈0.05） or monotheraphies. Compared with the saline treated EAE group, UTI combined methylprednisolone significantly increased expressions of CNP （1.14±0.06 vs. 0.65±0.04, P 〈0.001）, MBP （1.28±0.14 vs. 0.44±0.17, P 〈0.001）, and decreased expressions of proNGF （1.08±0.10 vs. 2.32±0.12, P 〈0.001）, p75 （1.13±0.13 vs. 2.33±0.17, P 〈0.001）, and iNOS （1.05±0.31 vs. 2.17±0.13, P 〈0.001） proteins in EAE. Furthermore, UTI combined methylprednisolone could significantly upregulate MBP （1.28±0.14 vs. 1.01±0.15, P 〈0.05） expression and downregulate iNOS （1.05±0.31 vs. 1.35±0.14, P 〈0.05） expression compared to methylprednisolone treatment EAE group. And proNGF expression was significantly lower in combined treatment （1.08±0.10） than that in UTI （1.51±0.24, P 〈0.05） or methylprednisolone （1.31±0.04, P 〈0.05） treatment group. Conclusion Combination treatment of UTI with methylprednisolone was shown to protect EAE, suggesting that combination therapy is a potential novel treatment in MS.
文摘Background Bilirubin is the end product of heme catabolism and has strong antioxidant properties. Serum bilirubin levels are reported to be reduced in patients with multiple sclerosis （MS） and neuromyelitis optica （NMO）. The pathophysiology of optic neuritis （ON） resembles that of MS; however, the role of endogenous bilirubin in ON is unclear. The aim of this study is to measure serum bilirubin levels in patients with ON, and to investigate the correlation between ON and serum antioxidant status of bilirubin. Methods Serum levels of bilirubin were measured in 42 patients with ON, 50 patients with multiple sclerosis （MS）, 48 patients with neuromyelitis optica （NMO） and 48 healthy control subjects. Results Serum total bilirubin （Tbil）, direct bilirubin （Dbil） and indirect bilirubin （Ibil） levels in patients with ON were significantly lower than those in the healthy controls. However, no statistical significance was found between levels in the ON and MS, ON and NMO, and MS and NMO groups. In patients with ON, serum Tbil, Dbil, and Ibil levels were lower in those with recurrence or those with ON for a longer duration （〉1 year）. Moreover, Tbil, Dbil, and Ibil concentrations were lower in patients with papillitis than in those with retrobulbar type ON, but the differences were not statistically significant. Conclusions Low antioxidant status may exist in patients with ON. But serum levels of Tbil, Dbil, and Ibil did not correlate with clinical presentations, such as recurrence, duration of disease and subtypes of ON. Low antioxidant status already existed in MS or NMO patients before systemic symptoms appeared.
文摘Voltage-gated potassium channels(VGKCs)represent a group of tetrameric signaling proteins with several functions,including modulation of neuronal excitability and neurotransmitter release.Moreover,VGKCs give a key contribution to the generation of the action potential.VGKCs are complexed with other neuronal proteins,and it is now widely known that serum autoantibodies directed against VGKCs are actually directed against the potassium channel subunits only in a minority of patients.By contrast,these autoantibodies more commonly target three proteins that are complexed with alpha-dendrotoxin-labeled potassium channels in brain extracts.These three proteins are contactin-associated protein-2(Caspr-2),leucine-rich,glioma inactivated 1(LGI-1)protein and the protein Tag-1/contactin-2.Neoplasms are detected only in a minority of seropositive patients for VGKC complex-IgG and do not significantly associate with Caspr-2 or LGI-1.Among all the cancers described in association with VGKC complex-IgG,lung carcinoma,thymoma,and hematologic malignancies are the most commonly detected.We will review all the major neurological conditions associated with VGKC complex-IgG.These include Isaacs’syndrome,Morvan syndrome,limbic encephalitis,facio-brachial dystonic seizures,chorea and other movement disorders,epilepsy,psychosis,gastrointestinal neuromuscular diseases,a subacute encephalopathy that mimics Creutzfeldt-Jakob prion disease both clinically and radiologically and autoimmune chronic pain.The vast majority of these conditions are reversible by immunotherapy,and it is becoming increasingly recognized that early diagnosis and detection of VGKC complex-IgG is critical in order to rapidly start the treatment.As a result,VGKC complex-IgG are now part of the investigation of patients with unexplained subacute onset of epilepsy,memory or cognitive problems,or peripheral nerve hyperexcitability syndromes.
文摘In recent years,anti-N-methyl-D-aspartate receptor(NMDAR)encephalitis overlapping with demyelinating disorders has attracted more and more attention.The case is about a 52-year-old woman with anti-NMDAR encephalitis presenting acute disseminated encephalomyelitis(ADEM)-like clinical/magnetic resonance(MR)findings.Here,the authors report this case and briefly review her MR evolution and the conditions of her prognosis.The recognition that patients with anti-NMDAR encephalitis may have demyelinating disorders,simultaneously or sequentially,is important.Otherwise,a high dose of steroid treatment with several courses could obtain good effect,even if given in the late phase.
文摘Objective To compare the clinical characteristics of CTD-LETM-NMOSD patients to CTD-LETM-non-NMOSD patients.Methods We retrospectively collected data from 40 CTD patients with LETM who were admitted to the Department of Neurology or Rheumatology at Peking Union Medical College Hospital from Jan,2006 to Dec,2016.
基金supported by the Innovative Antiviral Therapy Program,Leibniz Institute of Virology(LIV),the German Center for Infection Research(DZIF),EFRE 2014-2020 REACT-EU,Dutch Digestive Fund(MLDS CDG 15-02)Deutsche Forschungsgemeinschaft(BU 3630/2-1)+1 种基金Hüet Roëll Foundation.MK is supported by a Walter Benjamin Fellowship of the Deutsche Forschungsgemeinschaft(KA5554/1-1,KA5554/1-2)The Leibniz Institute of Virology is supported by the Free and Hanseatic City of Hamburg and the Federal Ministry of Health.
文摘Gastrointestinal infections are a major cause for serious clinical complications in infants.The induction of antibody responses by B cells is critical for protective immunity against infections and requires CXCR5+PD-1++CD4+T cells(TFH cells).We investigated the ontogeny of CXCR5+PD-1++CD4+T cells in human intestines.While CXCR5+PD-1++CD4+T cells were absent in fetal intestines,CXCR5+PD-1++CD4+T cells increased after birth and were abundant in infant intestines,resulting in significant higher numbers compared to adults.These findings were supported by scRNAseq analyses,showing increased frequencies of CD4+T cells with a TFH gene signature in infant intestines compared to blood.Co-cultures of autologous infant intestinal CXCR5+PD-1+/−CD4+T cells with B cells further demonstrated that infant intestinal TFH cells were able to effectively promote class switching and antibody production by B cells.Taken together,we demonstrate that functional TFH cells are numerous in infant intestines,making them a promising target for oral pediatric vaccine strategies.
