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.

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.

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.

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.

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.

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.

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.

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.

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.

Clinical efficacy and safety of single cycle rituximab as induction therapy for aggressive neuromyelitis optica spectrum disorder in a resource limited center: a preliminary study

Aim: To analyse the efficacy of single dose rituximab (RTX) as induction therapy followed by conventional oral steroid-sparing agents (azathioprine, mycophenolate mofetil or methotrexate) in a cohort of patients with aggressive neuromyelitis optica spectrum disorder (NMOSD) without CD19, 20 and 27 biomarker testing.Methods: A retrospective analysis of clinical outcomes in eight patients with aggressive NMOSD treated with one course of RTX induction therapy in the Neurology Department at Kuala Lumpur Hospital from 2005 to 2018 was performed. The effectiveness of the treatment was determined by the number of relapses, expanded disability status scale, annualized relapsed rates, and modified Rankin Scale both before and after treatment. B cell enumeration testing was done instead of CD19, 20 and 27 biomarker testing. Results: There was a reduction in the mean annualized relapse rate from 4.7 to 0.5 attacks per year after treatment (P = 0.011). Mean expanded disability status scale and modified Rankin Scale values improved from 5.4 to 3.6 (P = 0.018) and 3.6 to 2.6 (P = 0.023), respectively. No patient developed any adverse effect. Conclusion: Single-course RTX induction therapy regime may be an alternative therapeutic option in resource limited hospitals to suppress NMOSD disease activity in the short term as pulse induction therapy whilst awaiting the effectiveness of conventional steroid-sparing agents. Further prospectively designed studies are required to prove efficacy.

Interactions Between Extracellular Vesicles and Autophagy in Neuroimmune Disorders

Neuroimmune disorders,such as multiple sclerosis,neuromyelitis optica spectrum disorder,myasthenia gravis,and Guillain–Barrésyndrome,are characterized by the dysfunction of both the immune system and the nervous system.Increasing evidence suggests that extracellular vesicles and autophagy are closely associated with the pathogenesis of these disorders.In this review,we summarize the current understanding of the interactions between extracellular vesicles and autophagy in neuroimmune disorders and discuss their potential diagnostic and therapeutic applications.Here we highlight the need for further research to fully understand the mechanisms underlying these disorders,and to develop new diagnostic and therapeutic strategies.

Neuromyelitis Optica Spectrum Disorder Associated with Cervical Spondylosis

Neuromyelitis optica spectrum disease （NMOSD） refers to a group of related disease, in which potential pathogenesis is similar to neuromyelitis optica （NMO）, but clinical involvement does not exactly correspond to the diagnosis of NMO. Owing to varied clinical manifestations, it is apt to be misdiagnosed. We report a case of NMOSD with cervical spondylosis and discuss the experience of diagnosis.

Dawn of CAR-T cell therapy in autoimmune diseases

Chimeric antigen receptor(CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies.Based on the immunomodulatory capability of CAR-T cells,efforts have turned toward exploring their potential in treating autoimmune diseases.Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases,covering a range of subtypes such as systemic lupus erythematosus,multiple sclerosis,among others.CAR-T therapy holds promise in mitigating several shortcomings,including the indiscriminate suppression of the immune system by traditional immunosuppressants,and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints.By persisting and proliferating in vivo,CAR-T cells can offer a tailored and precise therapeutics.This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases,incorporating innovations well-studied in the field of hematological tumors,aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Neurofilament light chain in demyelinating conditions of the central nervous system: a promising biomarker

Neurofilaments are the major structural proteins of the neuronal cytoskeleton and are classified according to molecular weight into heavy,intermediate,and light chains.They are released into the interstitial fluid and cerebrospinal fluid(CSF)as a consequence of axonal damage.In particular,the light chain(NfL)represents the most abundant and soluble subunit and has been demonstrated to be increased in the CSF of patients with inflammatory,degenerative,vascular,or traumatic injuries in correlation with clinical and radiological activity.Similar results have been obtained measuring serum NfL with high-sensitivity single-molecule array,which enables reliable and repeatable measurement of the low NfL concentrations in serum.In particular,CSF and serum NfL values are strongly correlated in patients with multiple sclerosis(MS)and have been demonstrated to be increased in patients with MS and clinically isolated syndromes(CIS)in accordance with clinical and radiological activity.NfL levels increase in patients with a recent relapse and seem to predict cognitive impairment,long-term outcome,and conversion of CIS to MS.The few available data on patients with other demyelinating diseases suggest that NfL levels are also increased in neuromyelitis optica spectrum disorders and related conditions in correlation with attack severity,suggesting that axonal damage may occur in these disorders.We herein report and discuss published data on the role of NfL as a possible predictor of disease activity,clinical outcome and treatment response in patients with demyelinating conditions of the central nervous system.