Correlation of cognitive function with intracranial lesions and the degree of depression and anxiety in patients with neuromyelitis optica spectrum disorders / 中华内科杂志

Objective:To investigate the correlation of cognitive dysfunction with intracranial lesions and symptoms of depression and anxiety in patients with neuromyelitis optica spectrum disorders (NMOSD).Methods:Thirty-one NMOSD patients (7/24 males/females) were enrolled in the Department of Neurology of the Sixth Medical Center of the PLA General Hospital from August 2019 to August 2022. The average age was 42±13 years, and the average education level was 12 (9, 12) years. There were 30 healthy controls, 11/19 males/females, with an average age of 47±9 years and an average education of 12 (9, 15) years. The general clinical data and imaging data were collected, and the subjects were assessed on their cognition, anxiety and depression using the assessment scale approved at home and abroad. A cross-sectional study was conducted on them. The t-test or Wilcoxon test was used for inter-group comparison, and Pearson test or Spearman test was used to explore the correlation between the cognition of NMOSD patients and their intracranial lesions, depression and anxiety. Results:Compared with the healthy control group, NMOSD patients had significantly lower scores on MoCA ( Z=-3.10, P=0.002), CRAVLT-N7 ( Z=-5.12, P<0.001), CRAVLT-N8 ( t=-4.40, P<0.001), ROCF-R ( t=-3.10, P<0.01), ROCF-C ( Z=-2.72, P<0.01), PASAT-3 ( Z=-2.71, P<0.01), PASAT-2 ( Z=-3.14, P<0.01), and CWT-A ( Z=-3.10, P<0.01)scales. Frontal lobe lesions were negatively correlated with PASAT-2 ( r=-0.448, P=0.012) scores, temporal lobe lesions were negatively correlated with CRAVLT-N9 ( r=-0.564, P=0.001), and parietal lobe lesions were negatively correlated with MoCA ( r=-0.374, P=0.038), PASAT-3 ( r=-0.426, P=0.017), and PASAT-2 ( r=-0.459, P=0.009) scores; The scores of MoCA ( r=-0.392, P=0.029), CRAVLT-N6 ( r=-0.396, P=0.028), CRAVLT-N7 ( r=-0.415, P=0.020), CRAVLT-N8 ( r=-0.406, P=0.023), PASAT-3 ( r=-0.537, P=0.002) and PASAT-2 ( r=-0.495, P=0.005) scales were negatively correlated with the scores of HAMD assessment, and the scores of PASAT-3 ( r=-0.499, P=0.004) and PASAT-2 ( r=-0.452, P=0.011) were negatively correlated with the scores of HAMA. Conclusions:The cognitive function of patients with NMOSD is significantly reduced, involving multiple cognitive domains. The cognitive function is affected by the distribution of intracranial lesions and the degree of depression and anxiety.

CD4 + Th cell associated cytokines and neuromyelitis optica spectrum disease / 中华实验眼科杂志

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease characterized by neuro-ophthalmic intercross and humoral immunity.Neuromyelitis optica related optic neuritis (NMO-ON) is often the initial symptom of NMOSD patients, with a high blinding rate, which brought a heavy blow to the quality of life, study, work and other aspects of patients.The discovery of aquaporin-4 immunoglobulin G (AQP4-IgG) has brought significant progress in the pathogenesis, diagnosis and treatment of NMOSD.However, AQP4-IgG is not a universal biomarker of NMOSD.The role of CD4 + T helper (Th) cell related cytokines in the pathogenesis of NMOSD has been increasingly emphasized.This paper reviewed the research results of CD4 + Th cell-related cytokines closely related to the occurrence of NMOSD in recent years, including Th17 cell-related cytokines such as interleukin-6 (IL-6), IL-17, IL-21, Th2 cell-related cytokines such as IL-4, IL-5, IL-13, IL-31, IL-33, and regulatory T cell-related cytokines, etc.to provide new insights for the pathogenesis, diagnosis and treatment strategies of NMOSD or NMO-ON.

Neuromyelitis optica spectrum disorders / 中华神经科杂志

Neuromyelitis optica spectrum disorders (NMOSD) is an immune mediated inflammatory demyelinating disease of the central nervous system. Optic neuritis and longitudinally extensive transverse myelitis are the main clinical signs, and the etiology is mainly related to aquaporin 4 (AQP4) antibody. AQP4 is the target antigen of immune attack. NMOSD is characterized by optic neuritis, longitudinally extended transverse myelitis, medulla area postrema syndrome, brainstem syndrome, diencephalic syndrome and cerebral syndrome. In recent years, the etiological mechanism, clinical diagnosis and monoclonal antibodies targeting new mechanisms of NMOSD have made great progress, which promoted the development of clinical neurology.

Efficacy of mycophenolate mofetil for AQP4 antibody positive optic neuritis immunotherapy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To evaluate the efficacy of mycophenolate mofetil(MMF)on the prevention of relapse and visual prognosis of patients in neuromyelitis optica spectrum disorders(NMOSD)with AQP4 antibody positive optic neuritis. <p>METHODS: We retrospectively reviewed 11 patients with initial diagnosis of NMOSD and AQP4 antibody positive optic neuritis from January 2017 to December 2019. Among the 11 patients, 3 were male and 8 were female. The unique core clinical manifestation of NMOSD was optic neuritis. The onset age was 36.3±6.0(27-47)years old. Duration of the disease was 3.4±1.4(2.2-6.8)a. MMF was added in the relieving period of NMOSD for 1a or over 1a. Annualized relapsing rate(ARR), best corrected vision activity(BCVA)and adverse reactions of MMF were recorded.<p>RESULTS: The median time of MMF treatment was 18(12, 36)mo. The ARR was 0.66/a at baseline and 0.16/a after the treatment. There were 91% of the patients had decreased ARR and 82% of them had no clinical relapse. The patients had significant improvement on ARR after MMF treatment(<i>P</i><0.05 ). In total, there was no significant difference between the mean BCVA after treatment and that at baseline(<i>P</i>>0.05). Of the 11 patients, 3 patients had side effects(27%), including 1 patient with elevated liver transaminase(9%), and 2 patients with mild gastrointestinal reaction(18%)during follow-up period. None of them discontinued MMF due to adverse events.<p>CONCLUSION: MMF treatment for AQP4 antibody positive NMOSD can reduce the ARR of optic neuritis to a certain extent and protect the visual function of patients.

Research progress of sequential immunotherapy for neuromyelitis optica spectrum disorders in children / 中华实用儿科临床杂志

Pediatric neuromyelitis optica spectrum disorders (NMOSD) is an inflammatory demyelinating di-sease spectrum of the central nervous system, mainly involving the optic nerve and spinal cord.Due to the high disability and recurrence rate, sequential immunotherapy is usually needed to prevent the recurrence of NMOSD after acute treatment.Among the commonly used immune suppressants, Rituximab and Mycophenolate mofetil are the preferred drugs due to the best efficacy.Drug tolerance of Mycophenolate mofetil is better than that of Rituximab, and that of Cyclophosphamide remains the worst.Azathioprine is not recommended as the first-line drug of NMOSD because of frequent adverse events and the slow onset.This study aims to review the sequential immunotherapy of NMOSD in children.

Clinical Features of Neuromyelitis Optica Spectrum Disorders with Connective Tissue Diseases / 中国医学科学院学报

Objective To investigate the clinical features of neuromyelitis optica spectrum disorders(NMOSD)with connective tissue diseases(CTD). Methods Clinical data of 16 NMOSD-CTD patients and 54 NMOSD patients admitted to the Second Affiliated Hospital of Fujian Medical University from January 2015 to February 2020 were collected.The initial symptom,intracranial lesion,spinal cord lesion,laboratory examination and treatment response were compared between the two groups. Results The incidence of Sjögren's syndrome(SS)was the highest(10/16,62.5%)in NMOSD-CTD group.The NMOSD-CTD group had significantly higher positive rate of aquaporin-4 immunoglobulin G(AQP4-IgG)in serum or cerebrospinal fluid(100% vs. 70.2%,P=0.009),higher positive rates of serum anti-nuclear antibodies,anti Sjögren's syndrome A antibodies and anti-Ro52 autoantibodies(P0.05).Conclusions NMOSD is often complicated with CTD,and SS is the most common one.The positive rate of serum or cerebrospinal AQP4-IgG and the seropositivity of several other autoantibodies in NMOSD-CTD patients were higher than those in NMOSD patients.Neurological impairment in NMOSD-CTD patients were severer,which should arouse attention of clinicians.

Management of central nervous system demyelinating diseases during the coronavirus disease 2019 pandemic: a practical approach / Manejo de doenças desmielinizantes do sistema nervoso central na pandemia de doença do coronavírus 2019: uma abordagem prática

ABSTRACT Background: The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic. Objective: To discuss strategies to manage those patients. Methods: We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. Conclusions: In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.

RESUMO Introdução: A mais recente pandemia causada pelo coronavírus SARS-CoV-2 (COVID-19, do inglês coronavirus disease 2019) representa uma ameaça potencial para pacientes com doenças autoimunes, incluindo esclerose múltipla (EM) e transtorno do espectro de neuromielite óptica (NMOSD, do inglês neuromyelitis optica spectrum disorders). Esses pacientes são geralmente tratados com medicamentos imunomoduladores ou imunossupressores que podem alterar a resposta normal do organismo a infecções. Até o momento, não há consenso sobre como o manejo dos pacientes com EM e NMOSD deve ser realizado durante a pandemia. Objetivo: Discutir estratégias para manejar esses pacientes. Métodos: Focamos em como 1) reduzir o risco de infecção por COVID-19, como distanciamento social, telemedicina e exames laboratoriais e de imagem em intervalos mais amplos; 2) manejo de surtos, incluindo evitar tratamento de surto leve e uso de corticoide oral; 3) gerenciar terapias modificadoras de doença, como a preferência por medicamentos associados a menor risco de infecção (interferons, glatirâmer, teriflunomida e natalizumabe) e infusão em intervalo estendido de natalizumabe, quando seguro; 4) individualizar a escolha da terapia de indução para EM (anticorpos monoclonais anti-CD20, alentuzumabe e cladribina); 5) manejar terapias preventivas de NMOSD, incluindo seleção inicial de terapia e manutenção do tratamento atual; 6) manejar pacientes com EM/NMOSD que foram infectados por COVID-19. Conclusão: No futuro, séries de casos de pacientes com MS/NMOSD infectados com COVID-19 nos ajudará a definir as melhores estratégias de manejo. Por enquanto, contamos com a experiência e orientação especializadas.

Research status and progress of laboratory indexes related to neuromyelitis optica spectrum disorders / 解放军医学杂志

Neuromyelitis optica spectrum disorders (NMOSD) is a group of inflammatory demyelinating diseases of the central nervous system characterized by recurrent optic neuritis or long-segmental myelitis, with high recurrence and disability. The discovery of aquaporin 4-immunoglobulin G (AQP4-IgG) distinguished the disease from multiple sclerosis (MS) and became an independent disease. T cells, B cells and complement system were involved in NMOSD pathogenesis. The levels changed of many cytokines and complements components in NMOSD patients' serum and cerebrospinal fluid, and the levels of other related laboratory indexes such as serum uric acid (UA) and thyroid hormone has also changed dynamically. The research status and progress of some laboratory-related indexes other than AQP4-IgG for NMOSD patients were reviewed in present paper, in order to provide new ideas for clinical diagnosis and prognosis evaluation of NMOSD, and reduce the rates of missed diagnosis and misdiagnosis.

Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside / 神经科学通报·英文版

Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibody-mediated, inflammatory demyelinating disease of the central nervous system, characterized by optic neuritis and transverse myelitis. The binding of NMO-IgG with astrocytic aquaporin-4 (AQP4) functions directly in the pathogenesis of >60% of NMOSD patients, and causes astrocyte loss, secondary inflammatory infiltration, demyelination, and neuron death, potentially leading to paralysis and blindness. Current treatment options, including immunosuppressive agents, plasma exchange, and B-cell depletion, are based on small retrospective case series and open-label studies. It is noteworthy that monoclonal antibody (mAb) therapy is a better option for autoimmune diseases due to its high efficacy and tolerability. Although the pathophysiological mechanisms of NMOSD remain unknown, increasingly, therapeutic studies have focused on mAbs, which target B cell depletion, complement and inflammation cascade inactivation, blood-brain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy of mAb trials in NMOSD, including preclinical and experimental investigations.

Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders: From Bench to Bedside / 神经科学通报·英文版

Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) is a chronic, recurrent, antibody-mediated, inflammatory demyelinating disease of the central nervous system, characterized by optic neuritis and transverse myelitis. The binding of NMO-IgG with astrocytic aquaporin-4 (AQP4) functions directly in the pathogenesis of >60% of NMOSD patients, and causes astrocyte loss, secondary inflammatory infiltration, demyelination, and neuron death, potentially leading to paralysis and blindness. Current treatment options, including immunosuppressive agents, plasma exchange, and B-cell depletion, are based on small retrospective case series and open-label studies. It is noteworthy that monoclonal antibody (mAb) therapy is a better option for autoimmune diseases due to its high efficacy and tolerability. Although the pathophysiological mechanisms of NMOSD remain unknown, increasingly, therapeutic studies have focused on mAbs, which target B cell depletion, complement and inflammation cascade inactivation, blood-brain-barrier protection, and blockade of NMO-IgG-AQP4 binding. Here, we review the targets, characteristics, mechanisms of action, development, and potential efficacy of mAb trials in NMOSD, including preclinical and experimental investigations.

The characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders / 中华神经科杂志

Objective@#To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance.@*Methods@#The data about basic clinical features, fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs, 15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology, the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected. The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed. The relevance between the diversity of intestinal microbiota and inflammatory index was explored.@*Results@#Compared with healthy controls, the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered. The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls, while their inflammation indexes, including IL-6, IL-10 and transforming growth factor (TGF)-α, in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml, t=4.197, P=0.001; (3.4±2.1) pg/ml vs (0.9±0.2) pg/ml, t=2.265, P=0.037; (21.4±12.7) ng/ml vs (13.7±7.8) ng/ml, t=3.702, P=0.004). Compared with control group, the relative abundance of butyrivibrio, prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8%±3.5% vs 13.0%±4.7%, t=4.941, P<0.001; 3.9%±2.2% vs 6.9%±3.3%, t=3.282, P=0.003; 5.1%±2.5% vs 7.3%±3.0%, t=2.641, P=0.012), while the relative abundance of ackermania was increased obviously (7.0%±3.1% vs 4.4%±2.8%, t=2.802, P=0.008); Besides, the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4%±2.4% vs 5.5%±2.1%, t=2.784, P=0.009; 7.9%±5.4% vs 13.0%±4.7%, t=2.501, P=0.018). In the comparison between subgroups, the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1%±8.9% vs 32.6%±10.4%, t=2.572, P=0.016), while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4%±1.6% vs 1.7%±1.4%, t=2.977, P=0.006). Moreover, there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548, P=0.003).@*Conclusions@#The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs. Moreover, there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs, which can be used as an important means of clinical auxiliary examination.

The characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders / 中华神经科杂志

Objective To investigate the characteristics of intestinal microflora in patients with neuromyelitis optica spectrum disorders (NMOSDs) and related clinical significance.Methods The data about basic clinical features,fecal specimens as well as cerebrospinal fluid samples of 28 patients with NMOSDs,15 patients with multiple sclerosis (MS) and 16 healthy controls admitted to the Department of Neurology,the First Affiliated Hospital of Zhengzhou University from July 2017 to January 2019 were collected.The differences about intestinal microbial characteristics and inflammatory index levels in each group were analyzed.The relevance between the diversity of intestinal microbiota and inflammatory index was explored.Results Compared with healthy controls,the intestinal microfloras of patients with NMOSDs and MS respectively were structurally disordered.The levels of the microbial diversity (chao 1 index) were significantly decreased in patients with NMOSDs compared with healthy controls,while their inflammation indexes,including IL-6,IL-10 and transforming growth factor (TGF)-α,in cerebrospinal fluid were significantly increased ((12.9±4.6) pg/ml vs (2.6±1.8) pg/ml,t=4.197,P=0.001;(3.4±2.1) pg/ml vs (0.9±0.2)pg/ml,t=2.265,P=0.037;(21.4± 12.7) ng/ml vs (13.7±7.8) ng/ml,t=3.702,P=0.004).Compared with control group,the relative abundance of butyrivibrio,prevotella and anaerostipes was decreased significantly in NMOSDs group (6.8％±3.5％ vs 13.0％±4.7％,t=4.941,P＜0.001;3.9％±2.2％ vs 6.9％±3.3％,t=3.282,P=0.003;5.1％±2.5％ vs 7.3％±3.0％,t=2.641,P=0.012),while the relative abundance of ackermania was increased obviously (7.0％±3.1％ vs 4.4％±2.8％,t=2.802,P=0.008);Besides,the quantitative Streptococcus thermophilus and butyrivibrio reduced in MS group (3.4％±2.4％ vs 5.5％±2.1％,t=2.784,P=0.009;7.9％±5.4％ vs 13.0％±4.7％,t=2.501,P=0.018).In the comparison between subgroups,the relative abundance of bacteroides of aquaporin (AQP) 4-IgG-positive patients was lower than that of AQP4-IgG-negative patients (23.1％±8.9％ vs 32.6％± 10.4％,t=2.572,P=0.016),while the former subgroup had the higher level of the relative abundance of bifidobacterium (3.4％± 1.6％ vs 1.7％± 1.4％,t=2.977,P=0.006).Moreover,there was a significant relevance between the diversity of intestinal microflora and the level of inflammatory factor IL-6 in cerebrospinal fluid (r=-0.548,P=0.003).Conclusions The intestinal microflora structural disorder and diversity reduction exist in patients with NMOSDs.Moreover,there is a significant correlation between the intestinal microflora and the level of inflammatory factors in NMOSDs,which can be used as an important means of clinical auxiliary examination.

Neuromielitis óptica / Neuromyelitis optica

La neuromielitis óptica (NMO) es un trastorno autoinmune, inflamatorio y desmielinizante del sistema nervioso central con predilección por los nervios ópticos y médula espinal. En el año 2004 se publicó la asociación de NMO con un anticuerpo contra el canal de agua acuaporina 4 (anti-AQP4), como una enfermedad diferente de la esclerosis múltiple (EM). Actualmente se propone el término trastornos del espectro NMO (NMOSD), debido a que las manifestaciones de la enfermedad pueden ser más extensas, afectando además del nervio óptico y médula espinal, al área postrema del bulbo raquídeo, tronco encefálico, diencéfalo y áreas cerebrales típicas (periependimarias, cuerpo calloso, cápsula interna y sustancia blanca subcortical). NMOSD se aplica también a pacientes que cumplen los criterios de NMO y son negativos para anti-AQP4. Dentro de este último grupo se ha detectado en un 20% la presencia de otro anticuerpo, anti-MOG (Glicoproteína oligodendrocítica de mielina) con un mecanismo fisiopatológico diferente pero con una clínica, en algunos casos, similar, y en general con mejor pronóstico. El tratamiento inmunosupresor en la crisis, así como el tratamiento a largo plazo en los casos que esté indicado, es fundamental para evitar secuelas y recidivas. El diagnóstico correcto de esta entidad es fundamental ya que puede ser agravado con el uso de fármacos útiles en el tratamiento de EM. En esta publicación haremos una revisión de la fisiopatología, clínica y criterios diagnósticos de NMOSD, y discutiremos las distintas opciones terapéuticas.

Neuromyelitis optica (NMO) is an autoimmune, inflammatory and de myelinat ing disorder of the central nervous system with a predilection for the optic nerves and spinal cord. In 2004 the association of NMO with an antibody against the water channel aquaporin 4 (anti-AQP4) was published as a different pathology from multiple sclerosis (MS). Currently the term NMO spectrum disorders (NMOSD) is proposed, because the manifestations of the disease can be more extensive, affecting in addition to the optic nerve and spinal cord, the area postrema of the dorsal medulla, brainstem, diencephalon and typical brain areas (periependymal, corpus callosum, internal capsule and subcortical white matter). NMOSD is also applied to patients who meet the NMO criteria and are negative for AQP4-IgG. Within the latter group, the presence of another antibody, anti-MOG, has been detected in 20%, with a different physiopathological mechanism, but with a similar clinic and a better prognosis. The immunosuppressive treatment in the attack, as well as the long-term treatment in the cases that are indicated, is fundamental to avoid sequelaes and recurrences. The correct diagnosis of this entity is essential since it can be aggravated with the use of drugs useful in the treatment of MS. In this publication we will review the pathophysiology, clinical and diagnostic criteria of NMOSD, and discuss the different therapeutic options.

Correlation between blood-brain barrier permeability and physical disability in patients with neuromyelitis optica spectrum disorders / 上海交通大学学报（医学版）

Objective: To explore association between blood-brain barrier (BBB) permeability and physical disability in patients with neuromyelitis optica spectrum disorders (NMOSD). Methods: Clinical data of 105 patients with NMOSD was retrospectively analyzed in Department of Neurology at Changhai Hospital, Second Military Medical University and Renji Hospital, Shanghai Jiao Tong University School of Medicine from June 2009 to June 2016. According to the difference between the expanded disability status scale (EDSS) scores when discharged from hospital and when admitted to hospital, NMOSD patients were divided into disability-reduction group and disability-exacerbation group, and their clinical characteristics were compared between the two groups, then association between BBB permeability and physical disability was analyzed. Results: Between the disabilityreduction group and the disability-exacerbation group, there was no significant difference in gender, age, disease duration, inducing factor, clinical symptoms, and medication (all P>0.05), and the abnormal rates of thoracic spinal cord in clinical examination were statistically different (P=0.023). There was no significant difference in biochemical data between the two groups (P>0.05), and a statistically significant difference was observed in the rate of cerebrospinal/serum albumin ratio (QALB) in the cerebrospinal fluid examination (P=0.042). The percentages of exacerbation of disability in the QALB normal and high groups were 27.60% (16/58) and 46.80% (22/47), respectively, and there was a statistically significant difference between the two groups (χ2=4.150, P=0.042). BBB permeability was positively correlated with physical disability (r=0.299, P=0.042). Conclusion: The higher the BBB permeability of NMOSD patients on admission is, the higher the degree of physical disability is. The difference in BBB permeability provides key clues to the investigation of the immunological mechanisms of physical disability in NMOSD patients.

Lesions Caused by Intracerebral Injection of Aquaporin-4 Immunoglobulin G / 中山大学学报(医学科学版)

[Objective]To investigate the pathological damage caused by aquaporin-4 antibody extracted from patients with neuromyelitis optica spectrum disorders(NMOSD)and the influence of systemic immune status on the local disease focus.[Methods]The C57BL/6 mice were chose for establishing experimental autoimmune encephalomyelitis (EAE).During the peak at onset,serum-derived immunoglobulin G(IgG)from aquaporin-4(AQP4)IgG positive patients and healthy human complement(hC)were injected in the brain parenchyma(EAE+AQP4-IgG+hC group,n=5).The EAE induced mice injected with normal saline(EAE+NS group,n=5)and mice without EAE injected with AQP4-IgG and hC from healthy volunteers(AQP4-IgG + hC group,n=5)were served as control groups. The dramatic loss of AQP4,astrocyte glial fibrillary acidic protein(GFAP),oligodendrocyte myelin basic protein(MBP)and the infiltration of inflammatory cells(T lymphocytes,neutrophils and macrophages)were compared with each group by using immunoflu-orescence,in order to find abnormal changes.[Results]Intracerebral injection of AQP4-IgG together with hC can cause NMO-like lesions,including astrocyte injury,demyelination and inflammatory cell infiltration.However,EAE mice model with intracerebral injection of AQP4-IgG and hC represented more significant loss of AQP4 and GFAP(P=0.008 and P=0.016,respectively)compared with mice without EAE induced.The area of MBP loss was also increased,while there′s no statistical difference.No statistical difference was also found in the number of vessels infiltrated with CD3+T cell,neu-trophils and the area infiltrated with macrophage. Astrocyte proliferation existed in all groups,but no loss of AQP4, GFAP and MBP was found in EAE mice injected with NS.[Conclusion]Intracerebral injection of AQP4-IgG and hC can cause distinct pathological damage and the pathology can be promoted by immune system activated by EAE.Intracerebral injection of AQP4-IgG and hC can mimic the pathogenesis of NMOSD better in EAE mice model.

The role of aquaporin 4 antibody in the injury of retinal microstructure in neuromyelitis optica spectrum disorders / 中华内科杂志

Objective To evaluate the injury of retinal microstructure using optical coherence tomography (OCT) and investigate the role of aquaporin 4 antibody (AQP4 Ab) in this injury process.Methods Forty patients with neuromyelitis optica spectrum disorders (NMOSD) were retrospectively studied,each of whom reported at least one episode of optic neuritis (ON),namely 59 ON eyes involved in all.All patients were divided into two subgroups based on AQP4 Ab tests including 25 patients (37 ON eyes) with AQP4 positive (Ab+/NMOSD group) and 15 patients (22 ON eyes) negative (Ab-/NMOSD group).In addition,10 healthy controls (20 eyes) matched for age and sex (HC group) were analyzed.Spectral domain optical coherence tomography (SD-OCT) was used to quantify peripapillary retinal nerve fiber layer (RNFL).Nonparametric test was used to compare differences between groups.Results Age distribution and gender ratio were comparable in three groups (P＞0.05).Visual acuity in ON eyes of Ab+/NMOSD group was worse than that of Ab-/NMOSD group (P=0.02).There were no significant differences between Ab+/NMOSD and Ab-/NMOSD in aspects of disease duration (2.6 vs.1.9 year),ON episodes (2 vs.1),longitudinal extensive transverse myelitis (LETM) ratio (48.0％ vs.66.7％),NMOSD specific intracranial lesions ratio (32.0％ vs.53.3％),positive autoimmune antibody ratio (52.0％ vs.20.0％) (P=0.13,0.08,0.25,0.18,0.06,respectively).The thickness of temporal,superior,nasal,inferior and average RNFL in ON eyes of both Ab+/ NMOSD and Ab-/NMOSD group were thinner than those in eyes of HC group (all P＜0.05).The thickness of superior and inferior RNFL in ON eyes of Ab+/NMOSD were 61.0 μm and 62.0 μm,which was thinner than those of Ab-/NMOSD 94.5 μm and 97.0 μm (P=0.03 and 0.01,respectively).Conclusions RNFL reflects the injury of retinal microstructure in NMOSD patients.AQP4 Ab seropositivity is correlated to the severity of RNFL damage,implying the potential role of AQP4 Ab in this pathological process.

Clinical and imaging characteristics of pediatric neuromyelitis optica spectrum disorders / 中华实用儿科临床杂志

Objective To analyze the clinical and imaging characteristics of pediatric neuromyelitis optica spectrum disorders(NMOSD)in children. Methods The clinical data,imaging manifestations and follow - up data of 16 NMOSD patients at Department of Pediatric Neurology,Shandong Provincial Hospital Affiliated to Shandong Univer-sity between July 2013 and September 2017 were respectively analyzed. Results In 16 patients,initial presentations included optica neuritis(ON)in 5 cases,longitudinally extensive transverse myelitis(LETM)in 6 cases,and among them there were 2 cases with acute disseminated encephalomyelitis and 3 cases with both ON and LETM. Eleven cases received aquaporin - 4(AQP4)antibody examination and 4 cases were found seropositive. One case out of 7 detected cases was found AQP4 antibody positive in cerebrospinal fluid. Eleven cases received optica magnetic resonance imaging (MRI),and 8 cases were found abnormal signals in optic nerve and optica chiasma. The spinal cord MRI showed 13 ca-ses with LETM manifestations,and abnormal signals were found in vertebral segments(5 - 13),and among them 1 case had cervical cord,3 cases were thoracic cord and 9 cases were both of the above. Lesions in the cervical cord in 2 cases were extended upward to the medulla. Fifteen cases received brain MRI and all of them had brain lesions,which were mainly involved in the central and subcortical white matter,thalamus,corpus callosum,brainstem,the junction of spinal cord and medulla,cerebellum,and so on. All patients received treatment for acute attacks with high - dose Methylpred-nisolone and/ or gamma globulin and got obvious relief. Two cases with recurrent ON received treatment of Rituximab and their vision became improved. Fifteen patients were followed up,and 2 cases had limb disorders and 4 cases had visual impairment,other patients had no clinical symptoms. Conclusions Pediatric NMOSD has a diverse clinical pre-sentation at the onset disease. Those who are initial diagnosed acute myelitis,ON and acute disseminated encephalomye-litis should be considered the possibility of NMOSD. Antibody to AQP4 testing can assist the diagnosis. The typical ima-ging characters of NMOSD children are abnormal signals in the high expression area of AQP4. Intracranial lesions are more common in children. The acute treatment includes the high - dose Methylprednisolone and gamma globulin. Rituximab can be used for the recurrent patients.

Correlation between blood-brain barrier permeability and physical disability in patients with neuromyelitis optica spectrum disorders / 上海交通大学学报（医学版）

Objective· To explore association between blood-brain barrier (BBB) permeability and physical disability in patients with neuromyelitis optica spectrum disorders (NMOSD).Methods· Clinical data of 105 patients with NMOSD was retrospectively analyzed in Department of Neurology at Changhai Hospital,Second Military Medical University and Renji Hospital,Shanghai Jiao Tong University School of Medicine from June 2009 to June 2016.According to the difference between the expanded disability status scale (EDSS) scores when discharged from hospital and when admitted to hospital,NMOSD patients were divided into disability-reduction group and disability-exacerbation group,and their clinical characteristics were compared between the two groups,then association between BBB permeability and physical disability was analyzed.Results · Between the disabilityreduction group and the disability-exacerbation group,there was no significant difference in gender,age,disease duration,inducing factor,clinical symptoms,and medication (all P＞0.05),and the abnormal rates of thoracic spinal cord in clinical examination were statistically different (P=0.023).There was no significant difference in biochemical data between the two groups (P＞0.05),and a statistically significant difference was observed in the rate of cerebrospinal/serum albumin ratio (QALB) in the cerebrospinal fluid examination (P=0.042).The percentages of exacerbation of disability in the QALB normal and high groups were 27.60％ (16/58) and 46.80％ (22/47),respectively,and there was a statistically significant difference between the two groups (x2=4.150,P=0.042).BBB permeability was positively correlated with physical disability (r=0.299,P=0.042).Conclnsion · The higher the BBB permeability of NMOSD patients on admission is,the higher the degree of physical disability is.The difference in BBB permeability provides key clues to the investigation of the immunological mechanisms of physical disability in NMOSD patients.

The impact of pain, anxiety and depression on sleep quality in Chinese patients with neuromyelitis optica spectrum disorders

Background & Objective: Sleep quality in neuromyelitis optica spectrum disorders (NMOSD) were investigated in two recent studies. However, factors affecting sleep quality have not been studied in NMOSD. This study aimed to investigate the prevalence of sleep disorders in Chinese outpatient clinics with NMOSD and its clinical correlates. Methods: We administered Chinese validated self-questionnaires on HRQOL (MSQOL-54), sleep (PSQI), pain (SF-MPQ-2), anxiety (HARS) and depression (HDRS) to 42 patients followed up in our outpatient department. We assessed the relationships between sleep quality with pain, anxiety, depression, gender, age, disability, disease duration, NMO-antibody status and explored the determinants of poor sleep quality. Results: Sixty four percent of NMOSD patients were poor sleepers. Significant correlations were found between duration, disability, pain, anxiety, depression and sleep quality. Disability, depression and the domain of affective descriptors of pain were the three main predictors of poor sleep in NMOSD. Conclusion: This study reveals that poor sleep in NMOSD is common and it decreases physical function of quality of life. It is worthwhile considering exploring adjuvant strategies aimed at controlling pain associated affect, and treatment of depression may help to improve sleep quality in NMOSD.

Correlation study on elevated cholesterol level and the risk of relapse in patients with neuromyelitis optica spectrum disorders / 中国神经精神疾病杂志

Objective To explore the association between the cholesterol level and disease relapse in patients with Neuromyelitis Optica Spectrum Disorders (NMOSD). Methods Clinical and biochemical data of 96 patients with NMOSD were retrospectively analyzed. According to disease relapses, NMOSD patients were divided into primary and relapse groups.Their clinical characteristics and cholesterol level were compared between the two groups.The correlation between cholesterol level and disease recurrence was analyzed by partial correlation adjusted for sex. Results Between the primary group and relapse group,there were statistically significant differences in gender(48.8% vs. 80%, P<0.05), cholesterol (CHO)(4.27±0.85 vs. 5.18±1.26)and low density lipoprotein cholesterol (LDL-C)level[2.37(0.90)vs. 3.00 (1.21)](P<0.001). There were no significant difference in age, upper respiratory infection, gastrointestinal tract, rate of higher cerebrospinal fluid protein, triglyceride (TG)and high density lipoprotein cholesterol(HDL-C)(P>0.05). The percentage of recurrent patients in CHO normal and higher groups were 43.55% and 82.35% respectively, which was statistically significant difference between the two groups ( x2=13.51, P<0.01); The rate of relapse of LDL-C normal and higher groups were 47.69% and 75% respectively, which was statistically significant difference between the two groups ( x2=7.58,P<0.01).After adjusting for sex,CHO level was positively correlated with disease relapse(r=0.346,P<0.01),and LDL-C level also was positively correlated with disease relapse(r=0.380,P<0.01). Conclusion High CHO and LDL-C level may be associated with disease relapse, which has some clinical guiding significance for controlling CHO level in NMOSD patients.