Aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders:progress of experimental models based on disease pathogenesis

Neuromyelitis optica spectrum disorders are neuroinflammatory demyelinating disorders that lead to permanent visual loss and motor dysfunction.To date,no effective treatment exists as the exact causative mechanism remains unknown.Therefore,experimental models of neuromyelitis optica spectrum disorders are essential for exploring its pathogenesis and in screening for therapeutic targets.Since most patients with neuromyelitis optica spectrum disorders are seropositive for IgG autoantibodies against aquaporin-4,which is highly expressed on the membrane of astrocyte endfeet,most current experimental models are based on aquaporin-4-IgG that initially targets astrocytes.These experimental models have successfully simulated many pathological features of neuromyelitis optica spectrum disorders,such as aquaporin-4 loss,astrocytopathy,granulocyte and macrophage infiltration,complement activation,demyelination,and neuronal loss;however,they do not fully capture the pathological process of human neuromyelitis optica spectrum disorders.In this review,we summarize the currently known pathogenic mechanisms and the development of associated experimental models in vitro,ex vivo,and in vivo for neuromyelitis optica spectrum disorders,suggest potential pathogenic mechanisms for further investigation,and provide guidance on experimental model choices.In addition,this review summarizes the latest information on pathologies and therapies for neuromyelitis optica spectrum disorders based on experimental models of aquaporin-4-IgG-seropositive neuromyelitis optica spectrum disorders,offering further therapeutic targets and a theoretical basis for clinical trials.

Comparison of inebilizumab or rituximab in addition to glucocorticoid therapy for neuromyelitis optica spectrum disorders

AIM:To investigate the short-term efficacy and safety of inebilizumab for neuromyelitis optica spectrum disorders(NMOSD).METHODS:A total of 33 patients with NMOSD treated with inebilizumab(Group INB,n=15)or rituximab(Group RTX,n=18)in addition to high-dose glucocorticoids were included.Both groups underwent hormone shock therapy during the acute phase.Subsequently,Group INB received inebilizumab injections during the remission phase,while Group RTX received rituximab injections.A comparison of aquaporins 4(AQP4)titer values,peripheral blood B lymphocyte counts,and visual function recovery was conducted before and 8wk after treatment.Additionally,adverse reactions and patient tolerability were analyzed after using inebilizumab treatment regimes.RESULTS:Following inebilizumab treatment,there was a significantly improvement in the visual acuity of NMOSD patients(P<0.05),accompanied by a notable decrease in AQP4 titer values and B lymphocyte ratio(P<0.05).Moreover,inebilizumab treatment showed a partial effect in preventing optic nerve atrophy(P<0.05).However,there were no significant differences in other therapeutic effects compared to rituximab,which has previously demonstrated substantial therapeutic efficacy(P>0.05).Furthermore,inebilizumab exhibited higher safety levels than that of rituximab injections.CONCLUSION:The combination of inebilizumab and high-dose glucocorticoids proves to be effective.In comparison to rituximab injections,inebilizumab displays better tolerance and safety.Moreover,it demonstrates a partial effect in preventing optic nerve atrophy.Thus,it stands as an effective method to reduce the disability rates and improve the daily living ability of patients with NMOSD.

Clinical characteristics of patients with early-and late-onset optic neuromyelitis optica spectrum disease

Objective:To analyze the different clinical features of patients with early-onset(EO-NMOSDs)and late-onset neuromyelitis optica spectrum diseases(LO-NMOSDs).Methods:A total of 51patients with neuromyelitis optica spectrum disease who were diagnosed in our hospital for the first time from January 2015 to December 2022 were included in the First Affiliated Hospital of Hainan Medical College and divided into 22 cases in the EO-NMOSDs group and 29 cases in the LO-NMOSDs group according to whether the age of onset was 50 years old.The basic data,Extended Disability Status Scale(EDSS)score,blood and cerebrospinal fluid test indicators of the two groups were statistically analyzed.Results:There were no significant differences in demographic characteristics,clinical features and serum AQP-4 antibody positivity rate between the two groups(all P>0.05),and there were significant differences in triglycerides(TG),low-density lipoprotein(LDL),apolipoprotein A(APOA),apolipoprotein B(APOB)and lipoprotein a(P=0.010,P=0.048,P=0.014,P=0.061,P=0.001,respectively),and cerebrospinal fluid LDH,There were significant differences between microprotein quantification and EDSS score(P=0.018,P=0.034,P=0.025,respectively),and the level of microprotein quantification in cerebrospinal fluid of LO-NMOSDs had a certain correlation with the degree of disability(r=0.52,P<0.03).Conclusion:LO-NMOSDs and EO-NMOSDs group patients have similar demographic characteristics,serum AQP-4 antibody positive rate and clinical features,but compared with EO-NMOSDs,patients in LO-NMOSDs group are prone to abnormal lipid metabolism,higher trace proteins in cerebrospinal fluid and more likely to be disabled,and among LO-NMOSDs,the higher the trace protein in the cerebrospinal fluid,the more severe the disability status of patients.

Correlation between cerebral cortex changes and clinical features in patients with neuromyelitis optica spectrum disorder with normal-appearing brain tissue:a case-control study

Neuro myelitis optica spectrum disorder(NMOSD) is an inflammatory demyelinating disease of the central nervous system.However,whether and how cortical changes occur in NMOSD with normal-appearing brain tissue,or whether any cortical changes correlate with clinical chara cteristics,is not completely clear.The current study recruited 43 patients with NMOSD who had normal-appearing brain tissue and 45 healthy controls matched for age,sex,and educational background from December 2020 to February 2022.A surface-based morphological analysis of high-resolution T1-weighted structural magnetic resonance images was used to calculate the cortical thickness,sulcal depth,and gyrification index.Analysis showed that cortical thickness in the bilate ral rostral middle frontal gyrus and left superior frontal gyrus was lower in the patients with NMOSD than in the control participants.Subgroup analysis of the patients with NMOSD indicated that compared with those who did not have any optic neuritis episodes,those who did have such episodes exhibited noticeably thinner cortex in the bilateral cuneus,superior parietal co rtex,and pericalcarine co rtex.Correlation analysis indicated that co rtical thickness in the bilateral rostral middle frontal gyrus was positively correlated with scores on the Digit Symbol Substitution Test and negatively correlated with scores on the Trail Making Test and the Expanded Disability Status Scale.These results are evidence that cortical thinning of the bilateral regional frontal cortex occurs in patients with NMOSD who have normal-appearing brain tissue,and that the degree of thinning is correlated with clinical disability and cognitive function.These findings will help im prove our understanding of the imaging chara cteristics in NMOSD and their potential clinical significance.

Anti-glial fibrillary acidic protein antibody and anti-aquaporin-4 antibody double-positive neuromyelitis optica spectrum disorder:A case report

BACKGROUND A case of neuromyelitis optica spectrum disorder(NMOSD)with positive cerebrospinal fluid(CSF)anti-aquaporin-4 antibody(AQP4-IgG)and anti-glial fibrillary acidic protein IgG(GFAP-IgG)at the time of relapse was reported.The exact roles of GFAP-IgG in NMOSD are not fully understood and are the subject of ongoing research.This study revealed the possible connection between GFAPIgG and the occurrence or development of diseases.CASE SUMMARY A 19-year-old woman was admitted to the hospital due to a constellation of symptoms,including dizziness,nausea,and vomiting that commenced 1 year prior,reoccurred 2 mo ago,and were accompanied by visual blurring that also began 2 mo ago.Additionally,she presented with slurred speech and ptosis,both of which emerged 1 mo ago.Notably,her symptoms deteriorated 10 d prior to admission,leading to the onset of arm and leg weakness.During hospitalization,magnetic resonance imaging showed high T2-fluid attenuated inversion recovery signals,and slightly high and equal diffusion-weighted imaging signals.The serum antibody of AQP4-IgG tested positive at a dilution of 1:100.CSF antibody testing showed positive results for GFAP-IgG at a dilution of 1:10 and AQP4-IgG at a dilution of 1:32.Based on these findings,the patient was diagnosed with NMOSD.She received intravenous methylprednisolone at a daily dose of 500 mg for 5 d,followed by a tapering-off period.Afterward,the rate of reduction was gradually slowed down and the timely use of immunosuppressants was implemented.CONCLUSION The CFS was slightly GFAP-IgG-positive during the relapse period,which can aid in the diagnosis and treatment of the disease.

Biomarkers for neuromyelitis optica:a visual analysis of emerging research trends

Neuromyelitis optica is an inflammatory demyelinating disease of the central nervous system that differs from multiple sclerosis.Over the past 20 years,the search for biomarke rs for neuromyelitis optica has been ongoing.Here,we used a bibliometric approach to analyze the main research focus in the field of biomarkers for neuromyelitis optica.Research in this area is consistently increasing,with China and the United States leading the way on the number of studies conducted.The Mayo Clinic is a highly reputable institution in the United States,and was identified as the most authoritative institution in this field.Furthermore,Professor Wingerchuk from the Mayo Clinic was the most authoritative expe rt in this field.Keyword analysis revealed that the terms "neuro myelitis optica"(261 times), "multiple sclerosis"(220 times), "neuromyelitis optica spectrum disorder"(132 times), "aquaporin4"(99 times),and "optical neuritis"(87 times) were the most frequently used keywords in literature related to this field.Comprehensive analysis of the classical literature showed that the majority of publications provide conclusive research evidence supporting the use of aquaporin-4-IgG and neuromyelitis optica-IgG to effectively diagnose and differentiate neuromyelitis optica from multiple sclerosis.Furthermore,aquaporin-4-IgG has emerged as a highly specific diagnostic biomarker for neuromyelitis optica spectrum disorder.Myelin oligodendrocyte glycoprotein-IgG is a diagnostic biomarke r for myelin oligodendrocyte glycoprotein antibody-associated disease.Recent biomarkers for neuromyelitis optica in clude cerebrospinal fluid immunological biomarkers such as glial fibrillary acidic protein,serum astrocyte damage biomarkers like FAM19A5,serum albumin,and gammaaminobutyric acid.The latest prospective clinical trials are exploring the potential of these biomarkers.Preliminary results indicate that glial fibrillary acidic protein is emerging as a promising candidate biomarker for neuromyelitis optica spectrum disorder.The ultimate goal of future research is to identify non-invasive biomarkers with high sensitivity,specificity,and safety for the accurate diagnosis of neuro myelitis optica.

Association of GTF2IRD1–GTF2I polymorphisms with neuromyelitis optica spectrum disorders in Han Chinese patients

Variants at the GTF2I repeat domain containing 1(GTF2IRD1)–GTF2I locus are associated with primary Sj?gren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders(NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1–GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders(odds ratio(OR) = 1.364, 95% confidence interval(CI) 1.019–1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies(AQP4-IgG) positivity(OR = 1.397, 95% CI 1.021–1.912; P = 0.036) and stratification according to coexisting autoimmune diseases(OR = 1.446, 95% CI 1.072–1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients(OR = 3.15, 95% CI 1.183–8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China(approval number: 2016-31) on March 2, 2016.

Advances in research on neuromyelitis optica spectrum disorders and its clinical heterogeneity

Neuromyelitis optica spectrum disorders(NMOSD)is a demyelinating disease mainly involving the optic nerve and spinal cord.It has recurrent and aggravating attacks and high disability rate.Most patients have a stepwise progression,resulting in complete blindness or paraplegia.NMOSD lesions contain not only the optic nerve and spinal cord,but also other neurological and non-neurological symptoms,which has clinical heterogeneity.The discovery of aquaporin-4-immunoglobulin G(AQP4-IgG)attributed it to autoimmune ion-channel disease,and rituximab(RTX)has achieved good clinical efficacy in the treatment of NMOSD.Myelin oligodendrocyte glycoprotein(MOG)antibodies have been found in some AQP4-IgG-negative NMOSD patients,which have different clinical and immunological features,posing new challenges to the diagnosis and treatment of NMOSD,which may require re-design and testing of new immune-targeted drugs.

Report of a case of neuromyelitis optica spectrum disease with symptomatic epilepsy

Neuromyelitis optica spectrum disorder(NMOSD)is a humoral immune-mediated inflammatory demyelinating disease of the central nervous system with an unclear pathogenesis,often associated with autoimmune diseases such as systemic lupus erythematosus and dry syndrome.The pathology of the disease shows demyelinating changes and axonal damage,and the lesions mostly involve the optic nerve and spinal cord,and the last region of the medulla oblongata,thalamus,paraventricular,and other sites with high aquaporin-4 expression can also be involved.The clinical manifestations are closely related to the location of the lesion,with common symptoms such as optic neuritis,acute myelitis,and intractable eruption,and most patients have recurrent episodes that can leave sequelae such as visual impairment and urinary and bowel disorders.However,a few patients present with less common symptoms,which can easily be missed or misdiagnosed,delaying the diagnosis and treatment of the disease.In this paper,we report the case of a middle-aged female patient with the first symptoms of optic neuritis who developed seizures after 2 months.After completing relevant tests,cerebrospinal fluid and serum anti-aquaporin-4 antibodies were positive,and NMOSD with symptomatic epilepsy was considered.Seizures did not recur after hormone therapy was given again.The purpose of this report is to improve awareness and diagnosis of NMOSD among clinicians.

Review of Neuromyelitis Optica Spectrum Disorder with Pain-Depression Comorbidity

Neuromyelitis optica spectrum disorder(NMOSD)is an inflammatory disorder of the central nervous system predominantly targeting optic nerves and the spinal cord.The prevalence of the disease is much higher in Asia than in other parts of the world.Pain can be detected in more than 80%of NMOSD patients,with evoked pain mostly being caused by painful tonic muscle spasms and neuropathic pain as the most characteristic types.Depression is often comorbid with pain,and their comorbidity can severely influence quality of life.In recent years,studies have found considerable overlaps between the mechanisms of pain and depression;however,their association remains unclear.This article reviews the epidemiology,mechanism,evaluation and treatment of paindepression comorbidity in NMOSD patients.

Higher frequency of brain abnormalities in neuromyelitis optica spectrum disorder patients without primary Sjogren's syndrome

Neuromyelitis optica spectrum disorder often co-exists with primary Sjogreffs syndrome. We compared the clinical features of 16 neuro- myelitis optica spectrum disorder patients with （n = 6） or without primary Sjogreffs syndrome （n = 10）. All patients underwent extensive clinical, laboratory, and MRI evaluations. There were no statistical differences in demographics or first neurological involvement at onset between neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinudear autoantibody, anti-Sjogren＇s-syndrome-related antigen A an- tibodies, anti-Sjogren＇s-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sjogren＇s syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67% （4/6） of patients with primary Sjogren＇s syndrome and in 60% （6/10） of patients without primary Sj6gren＇s syndrome. More brain abnormalities were observed in patients without primary Sj6gren＇s syndrome than in those with primary Sj6gren＇s syndrome. Segments lesions （〉 3 centrum） were noted in 50% （5/10） of patients without primary Sj6gren＇s syndrome and in 67% （4/6） of patients with primary Sjogren＇s syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sjogren＇s syndrome are similar. However, neu- romyelitis optica spectrum disorder patients without primary Sjogreffs syndrome have a high frequency of brain abnormalities.

Rehabilitation and pharmacotherapy of neuromyelitis optica spectrum disorder:A case report

BACKGROUND Neuromyelitis optica spectrum disorder(NMOSD)is a demyelinating autoimmune disease that affects the central nervous system.It typically manifests as optic neuritis or extensive longitudinal myelitis,with or without the presence of anti-aquaporin protein 4 autoantibodies(immunoglobulin G).CASE SUMMARY We report the case of a 45-year-old woman with a history of Sjogren's syndrome who was diagnosed with NMOSD accompanied by spinal cord injury and left calf intermuscular vein thrombosis.The patient received hormone shock and gamma globulin therapy in the acute phase and standard rehabilitation treatment during convalescence.Upon discharge,the patient was able to control urination and defecation,stand independently,and walk short distances with the aid of a walker.CONCLUSION This case suggests that pharmacotherapy and standard rehabilitation treatment can improve the prognosis of NMSOD patients.

Serum LDL Promotes Microglial Activation and Exacerbates Demyelinating Injury in Neuromyelitis Optica Spectrum Disorder

Neuromyelitis optica spectrum disorder(NMOSD)is an autoimmune inflammatory demyelinating disease of the central nervous system(CNS)accompanied by blood-brain barrier(BBB)disruption.Dysfunction in microglial lipid metabolism is believed to be closely associated with the neuropathology of NMOSD.However,there is limited evidence on the functional relevance of circulating lipids in CNS demyelination,cellular metabolism,and microglial function.Here,we found that serum low-density lipoprotein(LDL)was positively correlated with markers of neurological damage in NMOSD patients.In addition,we demonstrated in a mouse model of NMOSD that LDL penetrates the CNS through the leaky BBB,directly activating microglia.This activation leads to excessive phagocytosis of myelin debris,inhibition of lipid metabolism,and increased glycolysis,ultimately exacerbating myelin damage.We also found that therapeutic interventions aimed at reducing circulating LDL effectively reversed the lipid metabolic dysfunction in microglia and mitigated the demyelinating injury in NMOSD.These findings shed light on the molecular and cellular mechanisms underlying the positive correlation between serum LDL and neurological damage,highlighting the potential therapeutic target for lowering circulating lipids to alleviate the acute demyelinating injury in NMOSD.

OCT及OCTA评估水通道蛋白-4抗体阳性NMOSD视网膜结构和血管密度及其与临床特征的关系

目的应用光学相干断层扫描(optical coherence tomography,OCT)及血管成像(optical coherence tomography angiography,OCTA)评价视神经脊髓炎谱系疾病(neuromyelitis optica spectrum disorders,NMOSD)视网膜结构和血管密度改变及其与临床疾病特征的相关性。方法共纳入水通道蛋白-4抗体阳性的NMOSD患者42例(84只眼),健康对照(对照组)45名(90只眼)。根据视神经炎(optic neuritis,ON)病史,NMOSD组进一步分为两组:有ON病史的NMOSD+ON组和无ON病史的NMOSD-ON组。通过OCT和OCTA测量神经节细胞复合体(ganglion cell complex,GCC)厚度、视网膜神经纤维层(retinal nerve fiber layer,RNFL)厚度、黄斑区浅层毛细血管丛(superficial capillary plexus,SCP)、深层毛细血管丛(deep capillary plexus,DCP)和视盘区血管的血管密度。记录患者NMOSD病程和发作次数、最佳矫正视力(best corrected visual acuity,BCVA)和扩展残疾状态量表(expanded disability status scale,EDSS)评分,分析上述指标与OCT和OCTA观察指标之间的相关性。结果黄斑和视盘的结构改变:与对照组比较,NMOSD+ON组总体及颞区(TEM)、上区(SUP)、鼻区(NAS)、下区(INF)各区的RNFL厚度均明显降低(P<0.05);NMOSD-ON组总体和SUP区的RNFL厚度明显降低(P<0.05)。与NMOSD-ON组比较,NMOSD+ON组总体及TEM、SUP、NAS、INF各区的RNFL厚度均明显降低(P<0.05)。与对照组比较,NMOSD+ON组总体、SUP及INF区的GCC厚度明显降低(P<0.05);NMOSD-ON组总体及SUP区的GCC厚度明显降低(P<0.05)。与NMOSD-ON组比较,NMOSD+ON组总体GCC厚度及SUP、INF区的GCC厚度明显降低(P<0.05)。黄斑区血管密度:与对照组比较,NMOSD+ON组SCP总体、中心凹、中心凹旁及中心凹周围TEM、SUP、NAS、INF各区血管密度均明显降低(P<0.05)。与对照组比较,NMOSD-ON组DCP总体血管密度、中心凹旁及中心凹周围TEM、SUP、NAS、INF各区血管密度均明显降低(P<0.05)。与NMOSD-ON组比较,NMOSD+ON组SCP总体血管密度以及中心凹旁TEM区、SUP区、INF区和中心凹周围TEM、SUP、NAS、INF各区血管密度均明显降低(P<0.05),DCP中心凹、中心凹旁NAS区、中心凹周围TEM区血管密度明显升高(P<0.05)。与对照组比较,NMOSD+ON组视盘区总体血管密度,视盘内血管密度以及和视盘旁鼻上区(NS)、鼻下区(NI)、下鼻区(IN)、下颞区(IT)、颞下区(TI)、颞上区(TS)、上颞区(ST)、上鼻区(SN)各区血管密度均明显降低(P<0.05)。与NMOSD-ON组比较,NMOSD+ON组除视盘内血管密度差异无统计意义(P=0.268)外,视盘区总体血管密度和视盘旁各区血管密度均明显降低(P<0.05)。NMOSD组病程与GCC厚度、RNFL厚度、SCP血管密度、放射状周围毛细血管(RPC)血管密度均呈负相关(分别r=-0.436,P<0.001;r=-0.337,P=0.002;r=-0.325,P=0.003;r=-0.239,P=0.028),发病次数与RNFL厚度、RPC血管密度呈负相关(分别r=-0.360,P=0.001;r=-0.315,P=0.004),BCVA与GCC厚度呈负相关(r=-0.303,P=0.005)。结论NMOSD患者发生和不发生ON的眼,均存在视网膜结构和视网膜血管的损伤,且NMOSD病程越长、发病次数越多,损伤越明显。与没有ON的眼相比,ON患眼SCP血管密度减低。

Macular microvascular and structural changes on optical coherence tomography angiography in atypical optic neuritis

BACKGROUND Atypical optic neuritis,consisting of neuromyelitis optica spectrum disorders(NMOSD)or myelin oligodendrocyte glycoprotein antibody disease(MOGAD),has a very similar presentation but different prognostic implications and longterm management strategies.Vascular and metabolic factors are being thought to play a role in such autoimmune neuro-inflammatory disorders,apart from the obvious immune mediated damage.With the advent of optical coherence tomography angiography(OCTA),it is easy to pick up on these subclinical macular microvascular and structural changes.AIM To study the macular microvascular and structural changes on OCTA in atypical optic neuritis.METHODS This observational cross-sectional study involved 8 NMOSD and 17 MOGAD patients,diagnosed serologically,as well as 10 healthy controls.Macular vascular density(MVD)and ganglion cell+inner plexiform layer thickness(GCIPL)were studied using OCTA.RESULTS There was a significant reduction in MVD in NMOSD and MOGAD affected as well as unaffected eyes when compared with healthy controls.NMOSD and MOGAD affected eyes had significant GCIPL thinning compared with healthy controls.NMOSD unaffected eyes did not show significant GCIPL thinning compared to healthy controls in contrast to MOGAD unaffected eyes.On comparing NMOSD with MOGAD,there was no significant difference in terms of MVD or GCIPL in the affected or unaffected eyes.CONCLUSION Although significant microvascular and structural changes are present on OCTA between atypical optic neuritis and normal patients,they could not help in differentiating between NMOSD and MOGAD cases.

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

Background： Neuromyelitis optica spectrum disorder （NMOSD） was long believed to be an aggressive form of multiple sclerosis （MS）. This study aimed to describe the clinical features of patients with MS and NMOSD to assist in differential diagnoses in clinical practice. Methods： Data including the patients＇ serum and cerebrospinal fluid （CSF） tests, image findings, and clinical information from 175 patients with MS or NMOSD at Xuanwu Hospital, Capital Medical University from November 2012 to May 2014 were collected and analyzed retrospectively. An enzyme-linked immunosorbent assay was performed to detect the myelin oligodendrocyte glycoprotein （MOG） autoantibodies in CSF and serum. Cell-based assays were used to detect aquaporin-4-antibody （AQP4-Ab）. The Chi-square test was used to compare the categorical variables. Wilcoxon rank sum test was peribrmed to analyze the continuous variables. Results： Totally 85 MS patients （49%） and 90 NMOSD patients （51%） were enrolled, including 124 （71%） women and 51 （29%） men. Fewer MS patients （6%） had autoinamune diseases compared to NMOSD （19%） （x2= 6.9, P 〈 0.01 ）. Patients with NMOSD had higher Expanded Disability Status Scale scores （3.5 [3]） than MS group （2 [2]） （x2= -3.69, P 〈 0.01）. The CSF levels of white cell count and protein in both two groups were slightly elevated titan the normal range, without significant difference between each other. Positivity of serum AQP4-Ab in NMOSD patients was higher than that in MS patients （MS： 0, NMOSD： 67%; x2= 63.9, P 〈 0.01 ）. Oligoclonal bands in CSF among NMOSD patients were remarkably lower than that among MS （MS： 59%, NMOSD： 20%; x2= 25.7, P 〈 0.01）. No significant difference of MOG autoantibodies was found between the two groups. Conclusion： The different CSF features combined with clinical, magnetic resonance imaging, and serum characteristics between Chinese patients with MS and NMOSD could assist in the differential diagnosis.

Monoclonal Antibody-Based Treatments for Neuromyelitis Optica Spectrum Disorders:From Bench to Bedside

Neuromyelitis optica(NMO)/NMO spectrum disorder(NMOSD)is a chronic,recurrent,antibodymediated,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,bloodbrain-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.

Prof.Ren ZHANG’s experience in acupuncture for neuromyelitis optica spectrum disorders

Prof.Ren ZHANG’s experience in clinical treatment of neuromyelitis optica spectrum disorders(NMOSD)is summarized in this paper.The pathogenesis of this kind of disease is complicated.Prof.Ren ZHANG treats it in both symptoms and root cause.In the acute stage and remission stage,based on the standard application of western medicines,acupuncture should be applied as early as possible and continued.In the acute stage,acupuncture can be an alternative and complementary treatment to reduce the adverse reaction of high dose hormone and shorten the acute course of this disease.In the remission stage,acupuncture can not only improve the visual function of patients,but also helps to retard the deterioration of this disease,reduce the recurrence and disability degree,having a long-term effect.The specific treatment method of Prof.Ren ZHANG emphasizes a combination of acupuncture and acupoint injection,with the extraordinary points as the main acupoints and coordinate with meridian acupoints in application.In the manipulation,it is emphasized deep insertion,penetrating method,and needling sensation to the diseased location.For the treatment course,it is emphasized that early intervention and long-term regular treatment.Here is the summarization of Prof.Ren ZHANG’s experience in treating this disease,which can be the reference for clinicians.

A comparative study of alteration in retinal layer segmentation alteration by SD-OCT in neuromyelitis optica spectrum disorders: A systematic review and meta-analysis

Background:To evaluate the feature of different retinal layer segmentation in neuromyelitis optica spectrum disorders(NMOSD)with spectral-domain optical coherence tomography(SD-OCT)and to compare it with that in multiple sclerosis(MS),healthy controls(HC),and idiopathic optic neuritis(ION).Methods:We retrieved four electronic databases,including Pubmed,Embase,Cochrane Library,and Web of Science from inception to September 1st,2021.A meta-analysis was performed to compare different retinal layer segmentation thicknesses between patients with or without a history of optic neuritis(ON)in NMOSD and the control group,including patients with MS,HC,and ION.Results:Forty-two studies were included and the interval between the last ON onset and examination was greater than 3 months.Compared with that in HC eyes,the loss of retinal nerve fiber layer(RNFL)and macular ganglion cell and inner plexiform layer(GC-IPL)was serious in NMOSD eye especially after ON.Moreover,compared with that in ION eyes or MS-related-ON eyes,the injury to the peripapillary retinal nerve fiber layer(pRNFL)was severe in NMOSD-related-ON eyes.In addition,the correlation coefficient between pRNFL and prognostic visual acuity was 0.43.However,the one-arm study revealed the inner nuclear layer(INL)was thickened in NMOSDrelated-ON eyes compared with HC eyes.Conclusions:Inclusion of the RNFL and macular GC-IPL is recommended for monitoring disease progression and attention should be paid to changes in the INL.

Current immunotherapies for multiple sclerosis and neuromyelitis optica spectrum disorders: the similarities and differences

Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are autoimmune demyelinating diseases of the central nervous system. Neuromyelitis optica was considered a variant of MS until the discovery of NMO-IgG in 2004, which changed our understanding of the pathophysiology of NMOSD. This review focuses on the similarities and differences in the immune treatments of MS and NMOSD.