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.

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.

Neuromyelitis Optica Revealed by Headache in a Child: A Case Report

Devic’s neuromyelitis optica (NMO) is a rare inflammatory disease of the central nervous system that results in optic neuropathy and myelitis. Optic neuritis represents the mode of entry into the disease in more than two thirds of cases. It is a rare entity in children. There is no effective treatment at present, but some molecules can be used, such as corticosteroids, immunosuppressants and plasma exchange. The prognosis in children is generally favorable. Devic’s neuromyelitis is a condition of unknown etiopathogeny which is functionally critical and requires early and appropriate treatment. We report the case of a 12-year-old girl who presented to emergency with a headache and decreased visual acuity, whose investigations led to the diagnosis of Devic’s neuromyelitis optica.

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.

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 Sj?gren's syndrome. We compared the clinical features of 16 neuromyelitis optica spectrum disorder patients with(n = 6) or without primary Sj?gren's 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 Sj?gren's syndrome. The laboratory findings of cerebrospinal fluid oligoclonal banding, serum C-reactive protein, antinuclear autoantibody, anti-Sj?gren's-syndrome-related antigen A antibodies, anti-Sj?gren's-syndrome-related antigen B antibodies, and anti-Sm antibodies were significantly higher in patients with primary Sj?gren's syndrome than those without. Anti-aquaporin 4 antibodies were detectable in 67%(4/6) of patients with primary Sj?gren's syndrome and in 60%(6/10) of patients without primary Sj?gren's syndrome. More brain abnormalities were observed in patients without primary Sj?gren's syndrome than in those with primary Sj?gren's syndrome. Segments lesions(> 3 centrum) were noted in 50%(5/10) of patients without primary Sj?gren's syndrome and in 67%(4/6) of patients with primary Sj?gren's syndrome. These findings indicate that the clinical characteristics of neuromyelitis optica spectrum disorder patients with and without primary Sj?gren's syndrome are similar. However, neuromyelitis optica spectrum disorder patients without primary Sj?gren's syndrome have a high frequency of brain abnormalities.

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.

Macular changes of neuromyelitis optica through spectral-domain optical coherence tomography

·AIM: To evaluate the thickness of the retinal layers in the macula using spectral-domain optical coherence tomography(SD-OCT) in patients with neuromyelitis optica(NMO).· METHODS: Spectralis SD-OCT, utilizing automated macular layer segmentation, was performed in 26 NMO patients and 26 healthy controls. Visual function including visual field tests and pattern visual evoked potential were recorded in study subjects.·RESULTS: Forty-one eyes from 26 NMO patients and52 eyes from 26 age- and sex-matched healthy controls were included. Besides total macular volume, peri-paipillary retinal nerve fiber layer(RNFL) thickness, the thickness of macular RNFL, ganglion cell layer(GCL) and inner plexiform layer(IPL) were also significantly reduced in NMO patients compared to those inhealthy controls(P <0.000). No differences were found in the thickness of macular inner nuclear layer(INL), outer plexiform layer(OPL), and outer nuclear layer(ONL) between the two groups. Reversely, the outer retinal layer(ORL) was shown to be thicker in NMO than controls(P <0.05).Compared with the peri-papillary RNFL thickness, the GCL thickness was demonstrated to correlate with visual function better.·CONCLUSION: The study provides in vivo evidence of retinal neural loss in NMO patients and demonstrates abetter structure-function correlation between retinal ganglion cell and visual function than peri-papillary RNFL does. In addition, no evidence of primary neural damage is found. Besides, the photoreceptor cells and retinal pigments epithelial(RPE) cells presumably proliferated in compensation in NMO after retinal neural loss.

Rituximab in neuromyelitis optica: A review of literature

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.

Neuromyelitis optica spectrum disorders and anti-myelin oligodendrocyte glycoprotein positive optic neuropathies

AIM: To describe the clinical characteristics and treatments associated with antibody positive optic neuropathies including anti-myelin oligodendrocyte glycoprotein(MOG) and anti-aquaporin 4(AQP4), alongside diagnostic modalities, investigations, and outcomes. METHODS: A cross-sectional single-centre retrospective case series consisting of 16 patients including 12 antiMOG positive patients and 4 anti-AQP4 positive patients. Each of these patients had clinical signs and symptoms of optic neuritis and consisted of all patients who had a positive blood antibody result in our centre. Clinical findings including presence of a relative afferent pupillary defect, colour vision and disc assessment were recorded. Structured clinical exam and multimodal imaging was undertaken sequentially on each. Optical coherence tomography(OCT) scanning was preformed to examine the correlation between ganglion cell layer(GCL) thickness and visual acuity(VA) at presentation and as a determinant of final visual outcome in both groups. Initial and long-term treatment is also summarised. RESULTS: A total of 16 patients were included in the study consisting of 12 anti-MOG and 4 anti-AQP4 positive patients. Nine of the 16 patients were female and the average age of onset was 29.2 y in the MOG group and 42 y in the AQP4 group. There was no statistically significant correlation(Pearson correlation) between GCL thickness and presenting and final VA [r(10)=0.081, P=0.08 and r(10)=0.089, P=0.34 respectively]. The same statistical analysis was performed for the correlation between retinal nerve fibre layer(RNFL) and VA and similar outcomes wereobserved [r(10)=0.04, P=0.22 and r(10)=0.09, P=0.04]. No correlation was seen for initial RNFL thickness and final visual outcome in this group either [r(2)=0.19, P=0.38]. Visual field testing and radiological findings for each group are described. CONCLUSION: No correlation between initial VA or RNFL and final visual outcome is identified. A broad range of visual field and radiographic findings are identified, a consensus on treatment of neuromyelitis optica spectrum disorders and anti-MOG positive optic neuropathies has yet to be accepted but initial high dose immunosuppression followed by low dose maintenance therapy is favoured.

Retinal ganglion cell-inner plexiform and nerve fiber layers in neuromyelitis optica

AIM: To determine the thickness of the retinal ganglion cell-inner plexiform layer(GCIPL) and the retinal nerve fiber layer(RNFL) in patients with neuromyelitis optica(NMO).METHODS: We conducted a cross-sectional study that included 30 NMO patients with a total of 60 eyes. Based on the presence or absence of optic neuritis(ON), subjects were divided into either the NMO-ON group(30 eyes) or the NMO-ON contra group(10 eyes). A detailed ophthalmologic examination was performed for each group; subsequently, the GCIPL and the RNFL were measured using highdefinition optical coherence tomography(OCT). RESULTS: In the NMO-ON group, the mean GCIPL thickness was 69.28±21.12 μm, the minimum GCIPL thickness was 66.02±10.02 μm, and the RNFL thickness were 109.33±11.23, 110.47±3.10, 64.92±12.71 and 71.21±50.22 μm in the superior, inferior, temporal and nasal quadrants, respectively. In the NMO-ON contra group, the mean GCIPL thickness was 85.12±17.09 μm, the minimum GCIPL thickness was 25.39±25.1 μm, and the RNFL thicknesses were 148.33±23.22, 126.36±23.45, 82.21±22.30 and 83.36±31.28 μm in the superior, inferior, temporal and nasal quadrants, respectively. In the control group, the mean GCIPL thickness was 86.98±22.37 μm, the minimum GCIPL thickness was 85.28±10.75 μm, and the RNFL thicknesses were 150.22±22.73, 154.79±60.23, 82.33±7.01 and 85.62±13.81 μm in the superior, inferior, temporal and nasal quadrants, respectively. The GCIPL and RNFL were thinner in the NMO-ON contra group than in the control group(P<0.05); additionally, the RNFL was thinner in the inferior quadrant in the NMO-ON group than in the control group(P<0.05). Significant correlations were observed between the GCIPL and RNFL thickness measurements as well as between thickness measurements and the two visual field parameters of mean deviation(MD) and corrected pattern standard deviation(PSD) in the NMO-ON group(P<0.05). CONCLUSION: The thickness of the GCIPL and RNFL, as measured using OCT, may indicate optic nerve damage in patients with NMO.

Clinical and pathological features of Devic’s neuromyelitis optica and multiple sclerosis in Chinese patients

BACKGROUND: Devic's neuromyelitis optica (DNMO) and multiple sclerosis in Asian populations have been considered to be the same disease. However, there is an increasing number of studies suggesting that DNMO and multiple sclerosis are different diseases. OBJECTIVE: Little information is available regarding comparisons of DNMO patients between China and other countries, as well as clinical manifestations of Chinese patients with DNMO and multiple sclerosis. The present study performed a multicenter, pathological, retrospective analysis. DESIGN, TIME AND SETTING: A retrospective analysis of clinical data from seven patients with DNMO diagnosed between 1957 and 1998. PARTICIPANTS: Data from Chinese DNMO patients was provided by the Shanghai Second Medical University, Sun Yat-sen University of Medical Sciences and the First Affiliated Hospital of Harbin Medical University in China. METHODS: Clinical and pathological data from Chinese patients with DNMO were retrospectively analyzed. The clinical characteristics of DNMO were compared between Chinese and Caucasian patients. In addition, clinical and pathological differences between DNMO and multiple sclerosis Chinese patients were compared. MAIN OUTCOME MEASURES: Clinical and pathological features of Chinese patients with DNMO. RESULTS: All seven Chinese patients with DNMO exhibited abrupt onset of vision disturbance, with a disease course of 3 days to 9 years. DNMO recurred in two of the patients. Demyelinating lesions were observed in all patients, with necrotic lesions and gitter cells in five patients, collagenous hyperplasia in one patient, and perivascular inflammatory cell infiltration in six patients. Comparison between Chinese and Caucasian DNMO patients revealed no significant differences in age at onset, clinical onset, duration, or interval between optic neuritis and myelitis. Compared with Chinese multiple sclerosis patients, Chinese DNMO patients presented with fewer recurrences, higher occurrence of necrosis, perivascular inflammatory cell infiltration and gitter cells, and a lower occurrence of collagenous hyperplasia. CONCLUSION: There was no difference in DNMO clinical features between Chinese and Caucasian patients. However, the clinical and pathological features of DNMO were different compared with multiple sclerosis in Chinese patients. Results suggested that the characteristics of DNMO in Chinese patients were significantly different than multiple sclerosis.

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.

Clinical effect of acupuncture combined with Chinese medicine on optic atrophy caused by neuromyelitis optica

Objective:To explore the clinical effect of acupuncture combined with traditional Chinese medicine on optic nerve atrophy caused by neuromyelitis optic(NMO).Methods:the patients with optic atrophy caused by NMO with optic neuritis who visited the ophthalmology or neuro-ophthalmology clinic of our hospital from March 2016 to December 2019 were collected.The patients were treated with acupuncture and traditional Chinese medicine for 8 weeks before and after treatment.The best corrected visual acuity and dynamic visual field were tested before treatment,4 weeks and 8 weeks after treatment,respectively,to evaluate the effect of acupuncture combined with traditional Chinese medicine on the visual function of patients;Results:after 4 weeks of treatment,the visual acuity of 8 eyes improved more than 2 lines,the total effective rate was 91.67%.after 8 weeks of treatment,the visual acuity of 12 eyes improved more than 2 lines,the total effective rate was 100%;after 4 weeks of treatment,the mean defect(MD)and mean sensitivity(MS)of dynamic visual field were improved,but the difference was not statistically significant(MD:t=1.579,P=0.121;MS:t=-1.500,P=0.140);after 8 weeks of treatment,the MD was significantly decreased(t=2.65,P<0.05),and the MS was significantly improved and statistically significant(t=-2.58,P<0.05).Conclusion:the combination of acupuncture and Chinese medicine can significantly improve the visual function of patients with optic atrophy caused by NMO,improve the best corrected visual acuity and dynamic visual field sensitivity,and reduce the visual field defect.

Clinical characteristics of 72 cases with neuromyelitis optical associated optic neuritis

Objective:To analyze the clinical characteristics of neuromyelitis optical associated optic neuritis(NMO-ON)patients,and to provide reference and basis for the prevention and treatment accordingly.Methods:The medical records of 72 NMO patients with ON as the first clinical manifestation in China-Japan Friendship Hospital from January 2016 to December 2019 were retrospectively analyzed and summarized,including general information,morbidity characteristics,course of disease,comorbid diseases,immunological tests,treatment response and prognosis,etc.Results:Totally 72 NMO-ON patients had a median age of 33 years.The ratio of male to female is about 1:5.54;The median course was 67 months,mainly"relapseremission".Totally 61.11% patients were successively involved in both eyes,the median incidence of ON was 2 times,and the median time of the second onset of ON was 3 months.The 1-year and 3-year recurrence rates were 55.56% and 73.61%,respectively.Around 91.67% of the patients had the onset of ON alone,and 81.94% of the patients had monocular involvement.About 19.44% patients were associated with inducement,the most common was upper respiratory tract infection;15.28% patients were associated with systemic immune diseases,most commonly associated with Sjogren's syndrome and thyroid diseases and 75.64% patients had first visual acuity less than 0.1,aquaporin-4 immunoglobulin G(AQP4-IgG)status(P=0.032,OR=2.55)and onset age(P=0.037,OR=3.93)were independent risk factors for first visual acuity.Up to the last follow-up time,the rate of unilateral blindness was about 48.61%,and the median of unilateral blindness ON was 2 times.Other nervous system involvement occurred in 73.61% of patients,and spinal cord(61.11%)was the most common site of recurrence.Serum AQP4-IgG was positive in 80.00%(48/60)of patients.A total of 18 cases(25.00%)were associated with other systemic immune antibodies,most commonly associated with ANA antibody positivity.Conclusions:The first onset of NMO-ON patients is mostly ON alone,with unilateral involvement and high incidence in young and middle-aged women.Bilateral optic nerve involvement and repeated recurrence are common in the long course of disease.AQP4-IgG status and onset age are independent risk factors affecting the visual function of NMO patients for the first onset,and most patients have positive AQP4-IgG serum.Some patients are associated with systemic immune diseases represented by Sjogren's syndrome and thyroid disease,which are at high clinical risk and require early diagnosis and treatment intervention.

Autoantibodies against myelin antigens in patients with neuromyelitis optica

In this study, we investigated the clinical relevance of anti-myelin antibodies in patients with neuromyelitis optica (NMO);titers of antibodies against myelin oligodendrocyte glycoproteins, proteolipid proteins and myelin basic proteins were measured in the sera of patients with NMO and compared to healthy controls, as well as to patients with other diseases. The frequency of presence of anti-myelin antibodies in patients with NMO was significantly higher than that in healthy and diseased controls. The expanded disability status scale scores correlated with the titers of the anti-myelin antibodies. Patients with anti-myelin antibody exhibited other autoantibodies significantly more frequently than patients without the antibody. Anti-myelin antibodies may be useful markers for predicting severe clinical courses in patients with NMO.

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.

Neuromyelitis optica and myelin oligodendrocyte glycoprotein

Neuromyelitis optica(NMO)refers to an antibody mediated,inflammatory disorder of the central nervous system(CNS)characterized by recurrent or monophasic attacks of optic neuritis and myelitis.Most patients with NMO possess a specific serum immunoglobin,NMO-IgG,which can serve as a biomarker for NMO.The autoantibodies target aquaporin-4(AQP4),the main water channel protein found in the CNS including the brain,spinal cord,and optic nerve.The remaining 10-25%of patients are seronegative for NMO-IgG despite meeting the diagnostic criteria for NMO.Recent studies have shown that a subset of these patients is seropositive for antibodies against myelin oligodendrocyte glycoprotein(MOG).This paper will provide an overview of the current English scientific literature published regarding the history,epidemiology,AQP4 biomarker,MOG biomarker,diagnosis,clinical features,related diseases in NMO spectrum disorder(NMOSD),and treatments of NMO.

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.