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.

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.

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.

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.

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.

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.

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.

Seropositivity rates of water channel protein 4 antibodies compared between a cell-based immunofluorescence assay and an enzyme-linked immunosorbent assay in neuromyelitis optica patients

A total of 66 samples （from 27 cases with neuromyelitis optica, 26 cases with multiple sclerosis, aa 13 cases with optic neuritis） were tested for aquaporin-4 antibody by a cell-based immunofluorescence assay and an enzyme-linked immunosorbent assay. The sensitivities and specificities of the two assays were similar. We further analyzed an additional 68 patients and 93 healthy controls using the enzyme-linked immunosorbent assay. A Kappa test showed good consistency between the two methods in terms of detection of anti-aquaporin-4 antibody in the se of neuromyelitis optica patients. No significant correlations were identified with onset age or disea duration, suggesting that aquaporin-4 antibody is a good marker for neuromyelitis optica. The enzyme-linked immunosorbent assay can be used for quantifying aquaporin-4 antibody concentrations and may be useful to dynamically monitor changes in the levels of aquaporin-4 antibody during disease duration.

Autologous mesenchymal stem cells applied on the pressure ulcers had produced a surprising outcome in a severe case of neuromyelitis optica

Recent studies provided evidence that mesenchymal stem cells（MSCs） have regenerative potential in cutaneous repair and profound immunomodulatory properties making them a candidate for therapy of neuroimmunologic diseases. Neuromyelitis optica（NMO） is an autoimmune, demyelinating central nervous system disorder characterized by a longitudinally extensive spinal cord lesion. A 46-year-old male diagnosed with NMO had relapses with paraplegia despite treatment and developed two stage IV pressure ulcers（PUs） on his legs. The patient consented for local application of autologous MSCs on PUs. MSCs isolated from the patient＇s bone marrow aspirate were multiplied in vitro during three passages and embedded in a tridimensional collagen-rich matrix which was applied on the PUs. Eight days after MSCs application the patient showed a progressive healing of PUs and improvement of disability. Two months later the patient was able to walk 20 m with bilateral assistance and one year later he started to walk without assistance. For 76 months the patient had no relapse and no adverse event was reported. The original method of local application of autologous BM-MSCs contributed to healing of PUs. For 6 years the patient was free of relapses and showed an improvement of disability. The association of cutaneous repair, sustained remission of NMO and improvement of disability might be explained by a promotion/optimization of recovery mechanisms in the central nervous system even if alternative hypothesis should be considered. Further studies are needed to assess the safety and efficacy of mesenchymal stem cells in NMO treatment.

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.

Detection of anti-aquaporin-4 autoantibodies in the sera of Chinese neuromyelitis optica patients

In this study, we recruited 10 neuromyelitis optica patients, two multiple sclerosis patients and two myelitis patients. Chinese hamster lung fibroblast （V79） cells transfected with a human aquaporin-4-mCherry fusion protein gene were used to detect anti-aquaporin-4 antibody in neuromyelitis optica patient sera by immunofluorescence. Anti-aquaporin-4 autoantibody was stably detected by immunofluorescence in neuromyelitis optica patient sera exclusively. The sensitivity of the assay for neuromyelitis optica was 90% and the specificity for neuromyelitis optica was 100%. The anti-aquaporin-4 antibody titers in sera were tested with serial dilutions until the signal disappeared. A positive correlation was detected between Expanded Disability Status Scale scores and serum anti-aquaporin-4 antibody titers. The anti-aquaporin-4 antibody assay is highly sensitive and specific in the sera of Chinese neuromyelitis optica patients. Detection of aquaporin-4 autoantibody is important for the diagnosis and treatment of neuromyelitis optica.

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 multi-center, 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 clays 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.

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.

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.

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.

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.