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Ever since interferon-β was introduced into China more than 20 years ago and used in the disease-modifying therapies (DMT) of multiple sclerosis (MS) patients, the Chinese translations of DMT used in China are quite puzzling, even clinicians are also difficult to understand the meaning of DMT. The authors searched and traced the origins of current DMT translations, which may be mainly due to the fact that the word "modifying" in Chinese contains two meanings: correction and alleviation, obviously currently used names prefer to correct, while the exact meaning of DMT should be to alleviate disease. Considering that inaccurate translation is widely used in domestic academic conferences and academic journals, it is easy to cause misunderstanding and ambiguity. The authors believe that the meaning of DMT should be correctly and deeply understood in the specific context, and the original meaning of alleviating disease should be returned, which is also in line with the two endpoints of immunomodulatory therapy for MS and optic neuromyelitis spectrum disease, the primary endpoint being to reduce the annual recurrence rate of the diseases, the secondary one being to slow the progression of disease disability.
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Objective The volume and cortical thickness of gray matter in patients with multiple sclerosis (MS) and neuromyelitis optica (NMO) were compared and analyzed by voxel⁃based morphometry (VBM) and surface⁃based morphometry (SBM), and the differences in the structural changes of gray matter in the two diseases were discussed. Methods A total of 21 MS patients, 16 NMO patients and 19 healthy controls were scanned by routine MRI sequence. The data were processed and analyzed by VBM and SBM method based on the statistical parameter tool SPM12 of Matlab2014a platform and the small tool CAT12 under SPM12. Results Compared with the normal control group (NC), after Gaussian random field (GRF) correction, the gray matter volume in MS group was significantly reduced in left superior occipital, left cuneus, left calcarine, left precuneus, left postcentral, left central paracentral lobule, right cuneus, left middle frontal, left superior frontal and left superior medial frontal (P<0. 05). After family wise error (FWE) correction, the thickness of left paracentral, left superiorfrontal and left precuneus cortex in MS group was significantly reduced (P<0. 05). Compared with the NC group, after GRF correction, the gray matter volume in the left postcentral, left precentral, left inferior parietal, right precentral and right middle frontal in NMO group was significantly increased (P<0. 05). In NMO group, the volume of gray matter in left middle occipital, left superior occipital, left inferior temporal, right middle occipital, left superior frontal orbital, right middle cingulum, left anterior cingulum, right angular and left precuneus were significantly decreased (P<0. 05). Brain regions showed no significant differences in cortical thickness between NMO groups after FWE correction. Compared with the NMO group, after GRF correction, the gray matter volume in the right fusiform and right middle frontal in MS group was increased significantly(P<0. 05). In MS group, the gray matter volume of left thalamus, left pallidum, left precentral, left middle frontal, left middle temporal, right pallidum, left inferior parietal and right superior parietal were significantly decreased (P<0. 05). After FWE correction, the thickness of left inferiorparietal, left superiorparietal, left supramarginal, left paracentral, left superiorfrontal and left precuneus cortex in MS group decreased significantly (P<0. 05). Conclusion The atrophy of brain gray matter structure in MS patients mainly involves the left parietal region, while NMO patients are not sensitive to the change of brain gray matter structure. The significant difference in brain gray matter volume between MS patients and NMO patients is mainly located in the deep cerebral nucleus mass.
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Abstract Precision medicine has revolutionized the field of neuroimmunology, with innovative approaches that characterize diseases based on their biology, deeper understanding of the factors leading to heterogeneity within the same disease, development of targeted therapies, and strategies to tailor therapies to each patient. This review explores the impact of precision medicine on various neuroimmunological conditions, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), optic neuritis, autoimmune encephalitis, and immune-mediated neuropathies. We discuss advances in disease subtyping, recognition of novel entities, promising biomarkers, and the development of more selective monoclonal antibodies and cutting-edge synthetic cell-based immunotherapies in neuroimmunological disorders. In addition, we analyze the challenges related to affordability and equity in the implementation of these emerging technologies, especially in situations with limited resources.
Resumo A medicina de precisão está revolucionando o campo da neuroimunologia, com uma abordagem inovadora caracterizada pela classificação de doenças com base em sua biologia, compreensão mais profunda dos fatores que levam à heterogeneidade dentro da mesma doença, desenvolvimento de terapias com alvos específicos e estratégias para adaptar as terapias a cada paciente. Esta revisão explora o impacto da medicina de precisão em várias condições neuroimunológicas, incluindo esclerose múltipla (EM), distúrbio do espectro da neuromielite óptica (NMOSD), doença associada ao anticorpo anti-glicoproteína da mielina do oligodendrócito (MOGAD), neurites ópticas, encefalites autoimunes e neuropatias imunomediadas. Discutimos avanços na subclassificação de doenças, reconhecimento de novas entidades, biomarcadores promissores e desenvolvimento de anticorpos monoclonais mais seletivos e imunoterapias de ponta baseadas em células sintéticas para as condições acima. Além disso, analisamos os desafios relacionados com acessibilidade e equidade na implementação dessas tecnologias emergentes, especialmente em ambientes com recursos limitados.
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Abstract Background There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. Objective To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. Methods A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. Results In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). Conclusion The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.
Resumo Antecedentes Há sobreposição clínica e radiológica entre as doenças desmielinizantes. No entanto, seus mecanismos fisiopatológicos são diferentes e apresentam prognósticos e demandas de tratamento distintos. Objetivo Investigar as características de imagens de RM dos pacientes com doença associada à glicoproteína de oligodendrócito de mielina (MOGAD), a doenças do espectro da neuromielite óptica positivas para antiaquaporina-4 imunoglobulina G (AQP4-IgG NMOSD), e pacientes duplamente soronegativos. Métodos Estudo retrospectivo e transversal para analisar as características e frequência das lesões do sistema nervoso central (SNC). Dois neurorradiologistas avaliaram consensualmente as imagens do cérebro, das órbitas e da medula espinhal. Resultados Ao todo, foram incluídos 68 pacientes(25 com AQP4-IgG NMOSD, 28 com MOGAD e 15 duplo-soronegativos). Há diferenças na apresentação clínica entre os grupos. O grupo MOGAD demonstrou menor frequência de comprometimento do cérebro (39.2%) comparado com o AQP4-IgG NMOSD (p = 0.002), com predomínio da distribuição das lesões nas regiões subcortical/justacortical, mesencéfalo, pedúnculos cerebelares médios e cerebelo. O grupo duplo-soronegativo demonstrou maior frequência de comprometimento do cérebro (80%), com lesões de maiores dimensões e com morfologia tumefeita, além de neurite óptica com maior extensão (p = 0.006). O grupo AQP4-IgG NMOSD demonstrou neurite óptica com predomínio na região óptico-quiasmática e as lesões encefálicas acometeram predominantemente as regiões hipotalâmica e área postrema (MOGAD versus AQP4-IgG NMOSD p = 0.013). Além disso, foram observadas mais lesões na medula espinhal (78.3%) e a presença da "bright spotty lesion" foi um achado primordial para a sua diferenciação com os pacientes MOGAD (p = 0.003). Conclusão A análise pormenorizada das características das lesões por RM dos pacientes com doenças desmielinizantes imunomediadas fornece informações fundamentais que auxiliam os médicos no diagnóstico diferencial em um momento oportuno.
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Abstract Plasma exchange (PLEX) is a therapeutic apheresis modality in which the plasma is separated from inflammatory factors such as circulating autoreactive immunoglobulins, the complement system, and cytokines, and its therapeutic effect is based on the removal of these mediators of pathological processes. Plasma exchange is well established for various neurological disorders, and it is applied successfully in central nervous system inflammatory demyelinating diseases (CNS-IDD). It mainly modulates the humoral immune system; thus, it has a greater theoretical effect in diseases with prominent humoral mechanisms, such as neuromyelitis optica (NMO). However, it also has a proven therapeutic effect in multiple sclerosis (MS) attacks. Several studies have suggested that patients with severe attacks of CNS-IDD have poor response to steroid therapy but show clinical improvement after the PLEX treatment. Currently, PLEX is generally established only as a rescue therapy for steroid unresponsive relapses. However, there are still research gaps in the literature regarding plasma volume, number of sessions, and how early the apheresis treatment needs to started. Thus, in the present article, we summarize the clinical studies and meta-analyses, especially about MS and NMO, outlining clinical data regarding the experience with therapeutic PLEX in severe attacks of CNS-IDD, the clinical improvement rates, the prognostic factors of a favorable response, and highlighting the likely role of the early apheresis treatment. Further, we have gathered this evidence and suggested a protocol for the treatment of CNS-IDD with PLEX in the routine clinical practice.
Resumo Plasmaférese (PLEX) é um procedimento em que o plasma é separado de fatores inflamatórios como imunoglobulinas autorreativas circulantes, sistema complemento e citocinas, e seu efeito terapêutico se baseia na remoção desses mediadores de processos patológicos. A PLEX está bem estabelecida no tratamento de diversos distúrbios neurológicos, e é utilizada com sucesso em surtos de doenças desmielinizantes inflamatórias do sistema nervoso central (CNS-IDD). A PLEX modula principalmente o sistema imunológico humoral; assim, tem efeito teórico maior em doenças com mecanismos patológicos humorais proeminentes, como a neuromielite óptica (NMO). No entanto tem também efeito terapêutico comprovado em surtos de esclerose múltipla (EM). Estudos sugerem que a corticoterapia é pouco eficaz em pacientes com surtos graves de CNS-IDD, e que estes apresentam melhora clínica após o tratamento com PLEX. Atualmente, a PLEX está geralmente estabelecida apenas como terapia de resgate para surtos não responsivos a corticosteroides. No entanto, há lacunas na literatura sobre a quantidade de troca de volume plasmático, o número de sessões, e o tempo de início da aférese terapêutica. Dessa forma, resumimos neste artigo estudos clínicos e metanálises, especialmente sobre EM e NMO, e delineamos os dados clínicos sobre a experiência com o uso de PLEX em surtos graves de CNS-IDD, as taxas de melhora clínica, os fatores prognósticos para uma resposta favorável, e destacamos o provável papel do tratamento precoce nestes casos. Em um segundo momento, reunimos essas evidências em uma sugestão de protocolo de tratamento de CNS-IDD com PLEX na prática clínica rotineira.
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RESUMEN INTRODUCCIÓN: El espectro de trastornos de neuromielitis óptica (NMOSD) es un grupo de enfermedades desmielinizantes, inflamatorias y autoinmunes, caracterizadas por episodios recurrentes de neuritis óptica y mielitis transversa longitudinal extensa, entre otras manifestaciones clínicas. Su tratamiento crónico se basa en el uso de terapias inmunosupresoras como azatioprina (AZA), micofenolato mofetilo (MFM) o rituximab (RTX). El objetivo del presente estudio es realizar un análisis comparativo de la respuesta al tratamiento con AZA o RTX. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, analítico, retrospectivo, en el cual se incluyeron inicialmente 69 pacientes con diagnóstico confirmado de NMOSD. Tras aplicar los criterios de inclusión y exclusión 59 pacientes fueron incluidos en el análisis final. RESULTADOS: En el grupo de RTX se evidenció una mejoría importante en el estado funcional en comparación con el grupo de AZA, en el que se vio un empeoramiento de este al año de seguimiento. El perfil de seguridad fue similar entre ambos grupos, con una adherencia significativamente superior en el grupo de RTX. DISCUSIÓN: Los hallazgos del presente estudio respecto a las ventajas del uso de RTX sobre AZA se encuentran en concordancia con resultados de estudios previos reportados en la literatura. CONCLUSIONES: Los resultados respaldan el uso de RTX sobre AZA como terapia de mantenimiento para pacientes con NMOSD, al estar asociado principalmente con una mejoría notable en la funcionalidad de los pacientes, al igual que una mayor adherencia al tratamiento.
ABSTRACT INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a group of inflammatory, autoimmune, and demyelinating disorders. Its hallmark behavior is characterized by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis, among other clinical manifestations. Chronic therapy is based primarily in immunosuppressive therapies such as azathioprine (AZA), mycophenolate mofetil (MMF), or rituximab (RTX). The goal of this study is to perform a comparative analysis of response rates to chronic treatment with either AZA or RTX. MATERIALS AND METHODS: A retrospective observational analytic study was designed with an initial cohort of 69 patients with a diagnosis of NMOSD. After application of the inclusion and exclusion criteria a total of 59 patients were finally included in the analysis. RESULTS: The RTX group had an improved functional status when compared to the AZA group; in the latter this feature worsened after a one-year follow-up. There was also a comparable safety profile between the two groups with a significantly greater adherence to RTX regimes. DISCUSSION: The findings of the current study as to the benefits of RTX in comparison to AZA are similar to the results of previous studies. CONCLUSION: These results favor the use of RTX as maintenance treatment of NMOSD, because of its greater benefit mainly in the improvement in functional status of patients, as well as a greater adherence to treatment.
Subject(s)
Azathioprine , Rituximab , Recurrence , Neuromyelitis OpticaABSTRACT
ABSTRACT Myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated optic neuritis has been established as a new entity of immune-mediated optic neuropathy. Patients usually present with recurrent optic neuritis, often bilaterally with initially severe vision loss and optic disc edema. However, in contrast to aquaporin 4-IgG-seropositive neuromyelitis optica spectrum disorder, visual recovery tends to be more favorable, with good response to steroid treatment. Another important differential diagnosis of myelin oligodendrocyte glycoprotein-IgG--associated optic neuritis is multiple sclerosis. Close monitoring for signs of relapse and long-term immunosuppression may be considered to maintain optimal visual function. The diagnosis can be made on the basis of the presence of a specific, usually serological, antibody against myelin oligodendrocyte glycoprotein (IgG; cell-based assay), and a demyelinating event (optic neuritis, myelitis, brainstem syndrome, or cortical lesions with seizures). The clinical spectrum of this newly recognized inflammatory demyelinating disease is expanding rapidly. We briefly review the epidemiological characteristics, clinical manifestations, diagnostic considerations, and treatment options of myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.
RESUMO A neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG foi estabelecida como uma nova entidade de neuropatia óptica imunomediada. Tipicamente os pacientes apresentam neurite óptica recorrente, muitas vezes bilateral, com perda de visão frequentemente severa e alta prevalência de edema do disco óptico na fase aguda. No entanto, em contraste com neuromyelitis optica spectrum disorder associada com presença de anticorpo contra aquaporina 4, a recuperação visual tende a ser mais favorável e responde bem ao tratamento com corticoide em altas doses. A esclerose múltipla representa outro importante diagnóstico diferencial de glicoproteína de oligodendrócito de mielina-IgG. O diagnóstico pode ser feito com base na presença de um anticorpo específico, geralmente sorológico contra glicoproteína de oligodendrócito de mielina (IgG, ensaio baseado em células), e presença de evento desmielinizante (neurite óptica, mielite, síndrome do tronco cerebral, lesões corticais com convulsões). O espectro clínico desta doença desmielinizante inflamatória recém-reconhecida está se expandindo rapidamente. Faremos uma breve revisão das características epidemiológicas, manifestações clínicas, considerações diagnósticas e opções de tratamento da neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG.
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Humans , Research Design , Optic Neuritis , Immunoglobulin G , Optic Neuritis/drug therapy , Myelin-Oligodendrocyte GlycoproteinABSTRACT
OBJECTIVE To indirectly compare and evaluate the efficacy and safety of rituximab， tocilizumab， eculizumab， inebilizumab and satralizumab in preventing the relapse of neuromyelitis optica spectrum disorders， so as to provide reference for clinical drug use. METHODS Retrieved from Embase， Medline， PubMed， CNKI， ClinicalTrials. gov， UMIN Clinical Trials Registry and Chinese Clinical Trial Registry， randomized controlled trials （RCTs） about five monoclonal antibodies （trial group） versus placebo or other therapeutic scheme （control group） were collected during the inception to Apr. 2022. Two reviewers independently screened literature， extracted data， and assessed the quality of included literature with Cochrane risk bias assessment tool. OpenBUGS software was used for network meta-analysis. In terms of safety， Chi-square test was performed for adverse events （AEs） in trial group and control group. RESULTS A total of 7 RCTs were included， involving 793 patients. The results of surface under the cumulative ranking curve （SUCRA） showed the order of capabilities decreasing relapse risk was： eculizumab＞ rituximab＞inebilizumab＞satralizumab； the order of capabilities reducing the annual recurrence rate was： eculizumab＞ satralizumab； the order of capabilities improving the progress of disability was： eculizumab＞satralizumab＞inebilizumab＞ rituximab＞tocilizumab. In terms of safety， the results of χ2 test showed that there were no statistically significant differences in the risk of total AEs and serious AEs in each study between trial groups and control groups （P＞0.05）； the incidence of infusion reaction， nausea and vomiting in rituximab group， and that of upper respiratory tract infection in eculizumab group were significantly higher than placebo group （P＜0.05）. CONCLUSIONS The effect of eculizumab is more optimal in three outcomes； in terms of improving the progress of disability， eculizumab， satralizumab and inebilizumab are more effective than the other two drugs； in terms of safety， there are significant goldenmoonsp@163.com differences in some AEs with different grades and individual AEs， but it is not found that they are inconsistent with the 学。E-mail：liyingpds@126.com reported results of the existing literature and drug instructions.
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Central nervous system involvement in primary Sjögren's syndrome (pSS) is less common and usually presents as white matter lesions, neuromyelitis optica spectrum disorder (NMOSD), or transverse myelitis. NMOSD is an immune-mediated inflammatory demyelinating disease of the central nervous system with a high rate of relapse and significant disability. Studies have shown that patients with pSS combined with NMOSD have more severe symptoms and poorer prognosis. Here, we present a case of critical illness in pregnancy-associated NMOSD combined with Sjögren's syndrome. The patient was a 30-year-old pregnant woman with a history of Sjögren's syndrome who was diagnosed with NMOSD. She received combination therapy with steroids, intravenous immunoglobulin (IVIG), and hydroxychloroquine during pregnancy, resulting in partial resolution of numbness below the waist. However, due to irregular medication adherence outside the hospital setting, she developed weakness in her right lower limb accompanied by inability to move it, while her left lower limb still had some mobility but occasional numbness along with urinary and fecal incontinence. Ten days later, she was admitted to the emergency department where an emergency cesarean section was performed to deliver a healthy baby boy. However, her condition worsened postpartum as she developed high fever accompanied by bilateral lower limb paralysis and weakness along with loss of voluntary control over urination and defecation. The patient underwent ano-ther course of treatment consisting of steroids and IVIG; however there was limited improvement in symptoms observed after this intervention. Following administration of rituximab for the first time, the patient developed urinary tract infection which was successfully managed before continuing regular infusions. In later stages the patient could walk slightly with a limp and regained control over urination and defecation, allowing her to resume normal activities. This case suggests that combination therapy with steroids, IVIG, and hydroxychloroquine should be considered for the patients with pregnancy-associated NMOSD combined with Sjögren's syndrome. Rituximab can significantly improve symptoms such as postpartum paralysis in patients with NMOSD, however, there may be a risk of infection associated with its use.
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Adult , Female , Humans , Pregnancy , Cesarean Section/adverse effects , Critical Illness , Hydroxychloroquine/therapeutic use , Hypesthesia/complications , Immunoglobulins, Intravenous/therapeutic use , Inflammation/complications , Neuromyelitis Optica/diagnosis , Paralysis/complications , Pregnancy Complications/therapy , Rituximab/therapeutic use , Sjogren's Syndrome/complications , Steroids/therapeutic use , Vision DisordersABSTRACT
Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system, primarily affecting the optic nerve and spinal cord.In addition to aquaporin 4 antibody, more and more studies have shown that interleukins (IL) also play an important role in the progression of NMOSD.For example, among the most common CD4 + T cells, Th17 cells can destroy the blood-brain barrier to invade the central nervous system and then affect autoimmunity; Th2-mediated IL-4 and IL-10 regulate immune activities by activating macrophages; Tregs can suppress the immune response by restricting various immune cell functions.The levels of related IL in the cerebrospinal fluid and blood of NMOSD patients vary at different stages of the disease course.This article mainly reviews the role and a change characteristics of interleukins related to NMOSD, which helps us to understand its pathogenic mechanism in-depth, and discusses whether IL can be used as immunophysiological markers to diagnose NMOSD.
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Objective:To compare the differences of brain activation in patients with neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) under contact heat stimulation (CHS), and to explore the characteristics of pain-related brain networks in NMOSD and MS patients.Methods:Fourteen NMOSD patients (NMOSD group) and 12 MS patients (MS group) admitted to Affiliated Hospital of North Sichuan Medical College from September 2022 to December 2022 who met the diagnostic criteria were collected. Twelve healthy individuals (HC group) matched with gender and age were recruited during the same period. Visual Analogue Scale (VAS) score was used to evaluate the pain of the subjects, CHS painful stimuli were given, and task-state functional magnetic resonance imaging (fMRI) scans were performed at the same time, and the differences in brain activation among the 3 groups were analyzed and compared.Results:(1) Compared with the HC group, the NMOSD group had a stronger activation degree than the HC group in the brain regions including the cortex around the left distance fissure, bilateral medial superior frontal gyrus; the activation degree of the NMOSD group was weaker than that of the HC group in the brain areas including the left medial and paracingulate gyrus, right superior parietal gyrus, left postcentral gyrus, and right supplementary motor area (all P<0.05). (2) Compared with the HC group, the brain regions whose activation degree was weaker in the MS group included the left caudate nucleus, left medial and paracingulate gyrus, left paracentral lobule, right superior parietal gyrus, left postcentral gyrus, left precuneus, right supplementary motor area, right superior temporal gyrus and right thalamus, and there was no brain area in the MS group whose activation degree was stronger than that of the HC group (all P<0.05). (3) Compared with the MS group, the brain regions with stronger activation degree in the NMOSD group included the left perifissure cortex and right thalamus, but no brain regions with weaker activation degree were found in the NMOSD group (all P<0.05). (4) There was a correlation between somatic pain VAS scores and activation of the medial superior frontal gyrus in the NMOSD group ( r=0.66, P<0.05). Conclusions:The results of CHS-fMRI in the NMOSD group, MS group and HC group showed that multiple brain regions were activated, indicating that multiple brain regions were involved in the generation and processing of pain, and there was a pain-related brain network. Pain-related brain networks were altered in NMOSD patients and MS patients, and there were differences in pain-related brain networks between the two diseases.
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Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune-mediated inflammatory demyelinating diseases of the central nervous system, characterized by optic nerve and spinal cord lesions, with high chance of recurrence and disability. Disease-modifying therapy, including immunosuppressants, monoclonal antibodies, stem cell transplantation etc., is the key to prevent recurrence. This article made a systematic review about the sequential treatment or prognosis of NMOSD by searching for the related articles published on PubMed from 2017 to 2022 to provide recommendations and references for disease-modifying therapy of NMOSD.
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@#Objective To investigate the clinical and neuroimaging features of adults with myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease at the first attack. Methods We retrospectively analyzed the clinical manifestations,radiological features,laboratory findings,and outcome of 14 adult patients with MOG antibody-associated disease at the first attack who were hospitalized in the departments of neurology of Jiangxi Provincial People's Hospital and Xinyu People's Hospital from January 2018 to January 2022. Results The 14 patients included six males and eight females,with a median age of 29.5 years. The most common initial symptoms were fever and headache (n=5),seizure (n=3),and dizziness (n=3). The supratentorial lesions were located in the thalamus (n=7),subcortical white matter (n=6),cortex (n=5),corpus callosum (n=2), and basal ganglia (n=2). The infratentorial lesions were frequently located in the brainstem:the pons (n=5),middle cerebellar peduncle (n=3),midbrain (n=2), and medulla (n=2). Three patients had spinal cord involvement,with one case of longitudinally extensive transverse myelitis. Thirteen patients had elevated cerebrospinal fluid cell counts,and seven had elevated cerebrospinal fluid protein levels. The serum MOG antibody titer ranged from 1∶3.2 to 1∶512. All the 14 patients received intravenous pulse glucocorticoid therapy. Only one patient had a relapse with optic neuritis. Conclusion In our study,MOG antibody-associated disease showed a slight female predominance and frequently presented as acute disseminated encephalomyelitis. The supratentorial lesions were often located in the thalamus and subcortical white matter,while the infratentorial lesions were frequently in the pons. Intravenous pulse steroid therapy was effecitve in the acute phase. The majority of the patients had a favorable outcome.
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Objective:To identify the potential intracranial inflammation in neuromyelitis optica spectrum disorders(NMOSD) patients without supratentorial MRI lesions using quantitative susceptibility mapping (QSM).Methods:Seventy NMOSD patients and 35 age- and gender-matched healthy controls (NC) underwent QSM, 3D-T 1, diffusion MRI from Beijing Tiantan Hospital during June 2019 to June 2021. Susceptibility was compared among NMOSD patients with acute attack (ANMOSD), NMOSD patients in chronic phase (CNMOSD) and NC. The correlation between susceptibility in several brain regions and the cerebrospinal fluid levels of inflammatory makers were analyzed. Results:NMOSD patients showed different susceptibility in several brain regions including bilateral hippocampus, precuneus, right cuneus, putamen, superior parietal and inferior temporal ( P<0.001) and the posr-hoc showed it is higher than normal. Compared to CNMOSD patients, the ANMOSD patients showed increased susceptibility in the cuneus (0.009 ± 0.004 vs. 0.005 ± 0.004, P<0.05). There was significant positive correlations between susceptibility and CSF levels of sTREM2 which reflect the active of microglial cells ( r = 0.494, P<0.05). Conclusions:Despite the absence of supratentorial lesions on MRI, increased susceptibility suggests underlying inflammation in the cerebral cortex in both patients with ANMOSD and CNMOSD, and some of them are obviously related to inflammatory markers in CSF. QSM sequence can be used to explore the potential inflammation in NMOSD patients without obvious supratentorial lesions.
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Objective:To evaluate the value of curative effect in neuromyelitis spectrum disease (NMOSD) based on circulatory function evaluation of intracerebral glymphatic system by using diffusion tensor imaging analysis along the perivascular space.Methods:The clinical and imaging data of 23 patients diagnosed with NMOSD at Tianjin Medical University General Hospital from March 2018 to December 2019 were retrospectively analyzed in this study. The clinical data included expanded disability status scale (EDSS), average relapse rate (ARR) and retinal nerve fiber layer (RNFL) thickness at baseline and 1 year follow-up after treatment. Among the 23 NMOSD patients, there were 22 females and 1 male, aged from 21 to 71 (45±13) years old. All the patients underwent MR scans at both baseline and 1 year after treatment, and the scanning sequences included cerebral 3D-T 1WI, T 2WI, diffusion tensor imaging and cervical spinal sagittal 3D-T 2WI, and the cervical spinal cord volume and bilateral diffusion tensor imaging analysis along the perivascular space index (ALPS index) were calculated. The partial correlation test was used to analyze the correlations between ALPS index and the clinical indicators such as EDSS, ARR, and bilateral RNFL, with the control variables as gender, age, years of education and course of disease. The multiple linear regression model was used to analyze the independent predictors for ALPS index and EDSS after treatment. Receiver operating characteristic curve (ROC) and area under the curve (AUC) were used to evaluate the diagnostic value of NMOSD treatment outcome by using ALPS index. Results:When controlling for gender, age, years of education and course of disease, there were significant negative correlations between right ALPS index and EDSS ( r=-0.50, P=0.048), bilateral average ALPS index and EDSS ( r=-0.53, P=0.034), left ALPS index and ARR ( r=-0.58, P=0.018), while there was significant positive correlations between right ALPS index and RNFL ( r=0.88, P=0.008) at 1 year follow-up after treatment. Multiple linear regression analysis showed that cervical spinal cord volume was an independent impact factor of bilateral average ALPS indexes (β=0.24, 95%CI 0.10-0.38, P=0.002), and bilateral average ALPS indexes (β=-3.22, 95%CI -5.97--0.48, P=0.024) and right RNFL (β=-0.05, 95%CI -0.08--0.02, P=0.002) at baseline were the independent impact factors of EDSS after treatment. ROC curve analysis showed that the bilateral average ALPS index at baseline had the best efficacy in predicting the curative effect of NMOSD patients with AUC=0.92. Conclusions:After treatment, NMOSD patients with severe clinical disability, high frequency of disease attack, poor visual performance, and severe cervical spinal cord atrophy have more serious impairment of intracerebral glymphatic system circulatory function. The ALPS index could help in predicting the clinical curative effect of NMOSD patients.
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Objective:To explore the different patterns of brain structural abnormalities in patients with delayed neuromyelitis optica pedigree disease (LO-NMOSD) and its relationship with clinical neuropsychological scale score based on the quantitative analysis of three-dimensional (3D) brain structure MRI.Methods:Patients with neuromyelitis optica pedigree disease in remission (NMOSD group) who received treatment at Jilin University First Hospital from January 2016 to December 2018 were prospectively included and divided into LO-NMOSD subgroup and early-onset NMOSD (EO-NMOSD) subgroup according to whether the age of first onset was>50 years. Another age-and sex-matched healthy volunteers with NMOSD patients were recruited as the control group. 3D brain T 1WI and T 2 fluid-attenuated inversion recovery sequence imaging were acquired, and clinical data, neuropsychological scores of all subjects were analyzed. Total gray matter volume (GMV), cerebral gray matter fraction (GMF), cerebral white matter fraction (WMF), and cerebral white matter high signal fraction (WMHF) were obtained by quantitative analysis of MRI data using voxel-based morphology and lesion segmentation tool techniques. Analysis of covariance was used to compare the differences in brain structure between LO-NMOSD subgroup and EO-NMOSD subgroup, NMOSD group and control group. Partial correlation analysis was used to analyze the correlation between GMF, WMHF and patient clinical data, neuropsychological scale scores, and the correlation between WMHF and GMF, WMF. Results:There were 47 cases in the NMOSD group, including 7 males and 40 females aged 18-66 years. Among them, there were 20 cases in the LO-NMOSD subgroup and 27 cases in the EO-NMODS subgroup. The control group consisted of 50 individuals (13 males and 37 females, aged 18 to 77 years). Compared with the control group, the GMV of the right caudate nucleus in the LO-NMOSD group was reduced ( t=3.33, P<0.05), and the GMV of multiple brain regions in the bilateral frontal and temporal lobes in the EO-NMOSD group was reduced considerably (FDR corrected, P<0.05), which was consistent with the NMOSD group. After adjusting for age, there was no statistically significant difference in WMHF between the LO-NMOSD and EO-NMOSD groups ( F=0.22, P=0.644). The LO-NMOSD subgroup showed a negative correlation between global GMF and the extended disability status scale (EDSS) score ( r=-0.53, P=0.025). WMHF in the NMOSD group was positively correlated with annual recurrence rate and EDSS ( r=0.35 and 0.35, respectively, and P=0.017 and 0.018, respectively), while other indicators were not correlated ( P>0.05). The EO-NMOSD subgroup WMHF showed a negative correlation with GMF and WMF ( r=-0.76, -0.70, respectively, P<0.001). The NMOSD group showed a negative correlation between WMHF and GMF, WMF ( r=-0.38, -0.55, respectively, P<0.05). There was no correlation between WMHF and GMF, WMF in the LO-NMOSD subgroup ( P>0.05). Conclusions:The extent and location of gray matter atrophy in patients with LO-NMOSD are different from those of EO-NMOSD. The correlation between WMHF and brain structural changes and clinical data is different between the two groups of patients. These suggest that LO-NMOSD patients may have different patterns of brain structural damage.
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Objective:To investigate the clinical and imaging differences between serum aquaporin 4 (AQP4) antibody positive and negative patients with neuromyelitis optica spectrum disorder (NMOSD).Methods:The clinical data and radiologic findings of 89 NMOSD patients diagnosed at Beijing Tiantan Hospital, Capital Medical University from January 2018 to June 2022 were retrospectively analyzed. There were 17 male cases and 72 female cases, aged 18-74 years. According to the results of serum AQP4 antibody test, the patients were divided into AQP4 antibody positive group and AQP4 antibody negative group, and the differences in clinical data, lesion distribution, lesion characteristics, and brain area volume between the 2 groups were compared using independent sample t-test and χ 2 test, and the correlation between brain area volume and expanded disability status scale (EDSS) scores was further investigated using Spearman correlation analysis. Results:There were 68 cases in the AQP4 antibody positive group and 21 cases in the AQP4 antibody negative group. Patients in both groups were predominantly female, but the percentage of females in the AQP4 antibody-positive group (86.8%, 59/68) was higher than that in the AQP4 antibody-negative group (61.9%, 13/21), with a statistically significant difference (χ 2=4.91, P=0.027). The incidence of optic neuritis in AQP4 antibody negative group (66.7%, 14/21) was higher than that in antibody positive group (41.2%, 28/68), with a statistically significant difference (χ 2=4.18, P=0.041). In the distribution of intracranial lesions on MRI, the probability of lesions involving the brain stem in AQP4 antibody negative group (47.6%, 10/21) was higher than that in AQP4 antibody positive group (23.5%, 16/68), the difference had statistically significance (χ 2=4.50, P=0.034). The volumes of whole brain white matter, right amygdala, right accumbens-area and right ventral diencephalon in AQP4 antibody positive group were lower than those in AQP4 antibody negative group ( P<0.05), and the volumes of the right accumbens-area were negatively correlated with the EDSS scores in AQP4 antibody positive group ( r=-0.628, P=0.009). Conclusion:There are differences in clinical and imaging manifestations between AQP4 antibody positive and AQP4 antibody negative patients, which provides more basis for clinical in-depth understanding of NMOSD.
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Objective:To investigate the correlation of cognitive dysfunction with intracranial lesions and symptoms of depression and anxiety in patients with neuromyelitis optica spectrum disorders (NMOSD).Methods:Thirty-one NMOSD patients (7/24 males/females) were enrolled in the Department of Neurology of the Sixth Medical Center of the PLA General Hospital from August 2019 to August 2022. The average age was 42±13 years, and the average education level was 12 (9, 12) years. There were 30 healthy controls, 11/19 males/females, with an average age of 47±9 years and an average education of 12 (9, 15) years. The general clinical data and imaging data were collected, and the subjects were assessed on their cognition, anxiety and depression using the assessment scale approved at home and abroad. A cross-sectional study was conducted on them. The t-test or Wilcoxon test was used for inter-group comparison, and Pearson test or Spearman test was used to explore the correlation between the cognition of NMOSD patients and their intracranial lesions, depression and anxiety. Results:Compared with the healthy control group, NMOSD patients had significantly lower scores on MoCA ( Z=-3.10, P=0.002), CRAVLT-N7 ( Z=-5.12, P<0.001), CRAVLT-N8 ( t=-4.40, P<0.001), ROCF-R ( t=-3.10, P<0.01), ROCF-C ( Z=-2.72, P<0.01), PASAT-3 ( Z=-2.71, P<0.01), PASAT-2 ( Z=-3.14, P<0.01), and CWT-A ( Z=-3.10, P<0.01)scales. Frontal lobe lesions were negatively correlated with PASAT-2 ( r=-0.448, P=0.012) scores, temporal lobe lesions were negatively correlated with CRAVLT-N9 ( r=-0.564, P=0.001), and parietal lobe lesions were negatively correlated with MoCA ( r=-0.374, P=0.038), PASAT-3 ( r=-0.426, P=0.017), and PASAT-2 ( r=-0.459, P=0.009) scores; The scores of MoCA ( r=-0.392, P=0.029), CRAVLT-N6 ( r=-0.396, P=0.028), CRAVLT-N7 ( r=-0.415, P=0.020), CRAVLT-N8 ( r=-0.406, P=0.023), PASAT-3 ( r=-0.537, P=0.002) and PASAT-2 ( r=-0.495, P=0.005) scales were negatively correlated with the scores of HAMD assessment, and the scores of PASAT-3 ( r=-0.499, P=0.004) and PASAT-2 ( r=-0.452, P=0.011) were negatively correlated with the scores of HAMA. Conclusions:The cognitive function of patients with NMOSD is significantly reduced, involving multiple cognitive domains. The cognitive function is affected by the distribution of intracranial lesions and the degree of depression and anxiety.
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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune demyelinating disease of the central nervous system characterized by the involvement of the optic nerve and spinal cord. The main clinical features are optic neuritis, acute myelitis, and area postrema syndrome. Aquaporin-4 (AQP4)-IgG-positive patients accounted for the majority and compared with AQP4-IgG-negative patients, the clinical symptoms were more severe, the recurrence was more frequent, and the disability rate was higher. The pathogenesis of AQP4-IgG-positive NMOSD is still not clear. This article reviews the research progress of the pathogenesis of AQP4-IgG-positive NMOSD.
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Dendritic cells are the most powerful antigen-presenting cells in the human body, which are involved in the occurrence and development of multiple sclerosis, neuromyelitis optica, myasthenia gravis and other neuroimmune conditions. Recently, tolerogenic dendritic cells (tolDCs) are gradually becoming the research focus and therapeutic target of neuroimmune conditions. They can reconstruct the balance of T cells by inducing effector T cell anergy/deletion, and producing antigen-specific regulatory T cells, ultimately achieving the goal of maintaining immune tolerance. In this review, the mechanisms that tolDCs reconstruct T cell balance in neuroimmune conditions are analyzed and the research progress related to tolDC therapy is summarized.