RESUMEN
BACKGROUND: The coexistence of neuromyelitis optica spectrum disorders (NMOSD) with other autoimmune diseases (AID) has been increasingly reported. The prevalence and significance of this association are not fully understood. OBJECTIVES: This study aimed to compare the clinical and laboratory characteristics in NMOSD patients with and without AID. METHODS: Retrospective cross-sectional observational study was conducted involving adults meeting NMOSD criteria followed in a neuroimmunology clinic at a tertiary center. Descriptive analysis of clinical/paraclinical/treatment/outcome data collected from the medical records was compared between NMOSD patients with AID (polyautoimmunity) and those without AID. RESULTS: From a cohort of 46 NMOSD patients, 16 (34.8 %) patients, mostly women around 40 years of age, presented with polyautoimmunity: 10 anti-AQP4 positive, 4 anti-MOG positive, and 2 seronegative. Five different organ -specific AID, and six systemic AID were identified in the polyautoimmunity patients group, in addition to 6 cases of multiple autoimmune syndrome. The AID manifestation preceded NMOSD in 10 (62.5 %) patients, with a median interval of 7 years. The NMOSD with polyautoimmunity and NMOSD without AID groups had similar initial clinical manifestations with optic neuritis and/or myelitis being most frequent. Inflammatory CSF, namely elevated proteins, was more common in the polyautoimmunity group (13.0 % in NMOSD vs. 31.3 % in NMOSD+AID, p = 0.003). After a 10±6 years follow-up period, more patients with polyautoimmunity had a relapsing disease (75.0 % in NMOSD vs. 46.7 % in NMOSD+AID, p = 0.012) but no difference in the functional outcome evaluated by the EDSS score was identified. CONCLUSIONS: Polyautoimmunity was common in AQP4 positive NMOSD patients leading to a significantly higher risk of disease recorrence. The presence of polyautoimmunity and multiple autoimmune syndrome in NMOSD patients suggests the existence of common susceptibility factors or pathophysiological mechanisms, emphasizing the importance of a multidisciplinary approach to those patients.
Asunto(s)
Neuromielitis Óptica , Humanos , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/epidemiología , Femenino , Adulto , Masculino , Estudios Transversales , Estudios Retrospectivos , Persona de Mediana Edad , Acuaporina 4/inmunología , Adulto Joven , Autoanticuerpos/sangreRESUMEN
OBJECTIVES: In myelin oligodendrocyte glycoprotein IgG-associated disease (MOGAD) and aquaporin-4 IgG+ neuromyelitis optica spectrum disorder (AQP4+NMOSD), the autoantibodies are mainly composed of IgG1, and complement-dependent cytotoxicity is a primary pathomechanism in AQP4+NMOSD. We aimed to evaluate the CSF complement activation in MOGAD. METHODS: CSF-C3a, CSF-C4a, CSF-C5a, and CSF-C5b-9 levels during the acute phase before treatment in patients with MOGAD (n = 12), AQP4+NMOSD (n = 11), multiple sclerosis (MS) (n = 5), and noninflammatory neurologic disease (n = 2) were measured. RESULTS: CSF-C3a and CSF-C5a levels were significantly higher in MOGAD (mean ± SD, 5,629 ± 1,079 pg/mL and 2,930 ± 435.8 pg/mL) and AQP4+NMOSD (6,017 ± 3,937 pg/mL and 2,544 ± 1,231 pg/mL) than in MS (1,507 ± 1,286 pg/mL and 193.8 ± 0.53 pg/mL). CSF-C3a, CSF-C4a, and CSF-C5a did not differ between MOGAD and AQP4+NMOSD while CSF-C5b-9 (membrane attack complex, MAC) levels were significantly lower in MOGAD (17.4 ± 27.9 ng/mL) than in AQP4+NMOSD (62.5 ± 45.1 ng/mL, p = 0.0019). Patients with MOGAD with severer attacks (Expanded Disability Status Scale [EDSS] ≥ 3.5) had higher C5b-9 levels (34.0 ± 38.4 ng/m) than those with milder attacks (EDSS ≤3.0, 0.9 ± 0.7 ng/mL, p = 0.044). DISCUSSION: The complement pathway is activated in both MOGAD and AQP4+NMOSD, but MAC formation is lower in MOGAD, particularly in those with mild attacks, than in AQP4+NMOSD. These findings may have pathogenetic and therapeutic implications in MOGAD.
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Acuaporina 4 , Activación de Complemento , Inmunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/líquido cefalorraquídeo , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/sangre , Acuaporina 4/inmunología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Glicoproteína Mielina-Oligodendrócito/inmunología , Inmunoglobulina G/líquido cefalorraquídeo , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Autoanticuerpos/líquido cefalorraquídeo , Autoanticuerpos/sangre , Anciano , Complemento C5a/líquido cefalorraquídeo , Complemento C5a/metabolismo , Complemento C5a/inmunología , Adulto Joven , Esclerosis Múltiple/líquido cefalorraquídeo , Esclerosis Múltiple/inmunología , Complemento C3a/metabolismo , Complemento C3a/líquido cefalorraquídeo , Complemento C3a/inmunología , Complejo de Ataque a Membrana del Sistema Complemento/metabolismo , Complejo de Ataque a Membrana del Sistema Complemento/líquido cefalorraquídeo , Complejo de Ataque a Membrana del Sistema Complemento/inmunologíaRESUMEN
It is known that certain human leukocyte antigen (HLA) genes are associated with autoimmune central nervous system (CNS) diseases, such as multiple sclerosis (MS), but their exact role in disease susceptibility and etiopathogenesis remains unclear. The best studied HLA-associated autoimmune CNS disease is MS, and thus will be the primary focus of this review. Other HLA-associated autoimmune CNS diseases, such as autoimmune encephalitis and neuromyelitis optica will be discussed. The lack of animal models to accurately capture the complex human autoimmune response remains a major challenge. HLA transgenic (tg) mice provide researchers with powerful tools to investigate the underlying mechanisms promoting susceptibility and progression of HLA-associated autoimmune CNS diseases, as well as for elucidating the myelin epitopes potentially targeted by T cells in autoimmune disease patients. We will discuss the potential role(s) of autoimmune disease-associated HLA alleles in autoimmune CNS diseases and highlight information provided by studies using HLA tg mice to investigate the underlying pathological mechanisms and opportunities to use these models for development of novel therapies.
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Modelos Animales de Enfermedad , Antígenos HLA , Ratones Transgénicos , Animales , Ratones , Humanos , Antígenos HLA/genética , Antígenos HLA/inmunología , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/genética , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/genética , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/genética , Enfermedades del Sistema Nervioso Central/inmunología , Enfermedades del Sistema Nervioso Central/genéticaRESUMEN
Neuromyelitis optica (NMO), which is also referred to as Devic's disease, was originally considered an aggressive subtype of multiple sclerosis (MS) presenting as optic neuritis and/or extensive transverse myelitis in which 50% of patients become blind or in a wheelchair within 5 years of onset. Subsequently, NMO was categorized as one of a spectrum of inflammatory and demyelinating autoimmune disorders that are distinct from multiple sclerosis and termed neuromyelitis optica spectrum disorder (NMOSD). NMOSD differs from multiple sclerosis by its clinical course, presentation, magnetic resonance imaging findings, clinical presentation, serum biomarker prognosis, and response to treatment. More recently, NMOSD has been subdivided according to auto-antibody status as aquaporin 4 (AQP4) seropositive NMO, myelin oligodendrocyte glycoprotein (MOG) antibody-associated disease (MOGAD), and seronegative NMOSD. The only treatment to date that has resulted in treatment-free remissions, now lasting for more than 5-10 years with posttreatment disappearance of anti-AQP4 antibodies, is hematopoietic stem cell transplantation (HSCT) using either an allogeneic (matched sibling or unrelated) donor with a reduced toxicity conditioning regimen or an autologous stem cell source using a nonmyeloablative conditioning regimen of plasmapheresis (PLEX), cyclophosphamide (Cytoxan®), rabbit antithymocyte (ATG), and rituximab (Rituxan®). Post-HSCT long-term resolution of disease activity and disappearance of AQP4 antibodies is consistent with HSCT-induced immune tolerance.
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Trasplante de Células Madre Hematopoyéticas , Neuromielitis Óptica , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/terapia , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Tolerancia Inmunológica , Acuaporina 4/inmunología , AnimalesRESUMEN
Autologous hematopoietic stem cell transplantation (aHSCT) may be effective in carefully selected pediatric patients with multiple sclerosis (MS), neuromyelitis optica (NMO), and chronic inflammatory demyelinating polyneuropathy (CIDP). aHSCT for pediatric MS (same as for adults) is performed to eradicate inflammatory autoreactive cells with lympho-ablative regimens and restore immune tolerance. Its therapeutic effect in MS relies on various mechanisms: (1) the immunosuppressive conditioning regimen prior to aHSCT was able to eradicate the autoreactive cells and (2) the regeneration/renewal of the immune system to reset the aberrant immune response against self-antigens. The aHSCT procedure includes the following different steps, as described in this chapter: patient selection through careful pretransplant screening, "wash-out" period from previous treatments, mobilization of hematopoietic stem cells (HSC), conditioning regimen, HSC infusion, and posttransplant monitoring for early and late complications. Moreover, specific aspects of pediatric population undergoing aHSCT are described. According to the available evidence, aHSCT appears to be safe in pediatric MS, obtaining disease control for a prolonged time after the procedure. A reasonable approach in this setting includes the application of less toxic treatments while reserving aHSCT procedure for patients with severe/refractory forms of the disease. The EBMT considers MS, NMO, and CIDP in pediatric patients within the category of the clinical option (CO), where candidates for aHSCT can be selected on the basis of careful consideration of individual case history in the multidisciplinary setting.
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Trasplante de Células Madre Hematopoyéticas , Trasplante Autólogo , Humanos , Trasplante de Células Madre Hematopoyéticas/métodos , Niño , Trasplante Autólogo/métodos , Enfermedades Autoinmunes del Sistema Nervioso/terapia , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Neuromielitis Óptica/terapia , Neuromielitis Óptica/inmunología , Pediatría/métodosRESUMEN
Aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) is an autoimmune disease characterized by suboptimal recovery from attacks and long-term disability. Experimental data suggest that AQP4 antibodies can disrupt neuroplasticity, a fundamental driver of brain recovery. A well-established method to assess brain LTP is through intermittent theta-burst stimulation (iTBS). This study aimed to explore neuroplasticity in AQP4-NMOSD patients by examining long-term potentiation (LTP) through iTBS. We conducted a proof-of-principle study including 8 patients with AQP4-NMOSD, 8 patients with multiple sclerosis (MS), and 8 healthy controls (HC) in which iTBS was administered to induce LTP-like effects. iTBS-induced LTP exhibited significant differences among the 3 groups (p: 0.006). Notably, AQP4-NMOSD patients demonstrated impaired plasticity compared to both HC (p = 0.01) and pwMS (p = 0.02). This pilot study provides the first in vivo evidence supporting impaired neuroplasticity in AQP4-NMOSD patients. Impaired cortical plasticity may hinder recovery following attacks suggesting a need for targeted rehabilitation strategies.
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Acuaporina 4 , Neuromielitis Óptica , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Acuaporina 4/metabolismo , Acuaporina 4/inmunología , Femenino , Neuromielitis Óptica/fisiopatología , Neuromielitis Óptica/inmunología , Adulto , Masculino , Persona de Mediana Edad , Corteza Cerebral/fisiología , Plasticidad Neuronal/fisiología , Proyectos Piloto , Potenciación a Largo Plazo/fisiología , Autoanticuerpos/inmunologíaRESUMEN
Autoantibodies are the cause of the chronic inflammatory diseases known as neuromyelitis optica spectrum disorders (NMOSD). Serum antibodies (Abs) that specifically target the aquaporin-4 (AQP-4) water channel are the cause of recurrent episodes of optic neuritis, myelitis, and/or brain stem disorders. In contrast to AQP-4 Abs, myelin oligodendrocyte glycoprotein (MOG) Abs are detected in some patients exhibiting nonmotor cognitive impairment. These days, the term "MOG-encephalomyelitis" (MOG-EM) is frequently used to describe these clinical syndromes. The diagnosis of these cases involves the use of magnetic resonance imaging, optical coherence tomography, antibody detection, and additional laboratory testing. By detecting the patient's Abs in their serum or cerebrospinal fluid (CSF), indirect immunofluorescence (IIF) aids in the proper diagnosis. We highlight five NMOSD cases where serum anti-MOG antibody positivity was found using IIF, but CSF was not. In none of the cases, anti-AQP Abs were found. Effective patient management strategies include the treatment of acute attacks and long-term immunosuppressive drugs such as rituximab, azathioprine, and immunoglobulins. IIF is a quick and easy tool to detect anti-MOG Abs in patients with NMOSD/myelin oligodendrocyte glycoprotein antibody-associated disorder. CSF testing for MOG or AQP-4 Abs is not usually advised. It does not offer additional benefits to help with MOG-EM or NMOSD diagnosis.
RésuméLes autoanticorps sont à l'origine de maladies inflammatoires chroniques connues sous le nom de troubles du spectre de la neuromyélite optique (NMOSD). Sérum les anticorps (Abs) qui ciblent spécifiquement le canal hydrique de l'aquaporine-4 (AQP-4) sont à l'origine d'épisodes récurrents de névrite optique, de myélite, et/ou des troubles du tronc cérébral. Contrairement aux Abs AQP-4, les Abs glycoprotéines oligodendrocytes de myéline (MOG) sont détectés chez certains patients présentant déficience cognitive non motrice. De nos jours, le terme « MOG encéphalomyélite ¼ (MOG-EM) est fréquemment utilisé pour décrire ces troubles cliniques syndrome. Le diagnostic de ces cas fait appel à l'imagerie par résonance magnétique, à la tomographie par cohérence optique, à la détection d'anticorps, et des tests de laboratoire supplémentaires. En détectant les Abs du patient dans son sérum ou liquide céphalo-rachidien (LCR), immunofluorescence indirecte (IIF) aide au bon diagnostic. Nous mettons en évidence cinq cas de NMOSD où la positivité des anticorps anti-MOG sériques a été trouvée en utilisant l'IIF, mais le LCRn'était pas. Dans aucun des cas, des Ac anti-AQP n'ont été trouvés. Les stratégies efficaces de prise en charge des patients comprennent le traitement des crises aiguës et médicaments immunosuppresseurs à long terme tels que le rituximab, l'azathioprine et les immunoglobulines. IIF est un outil simple et rapide pour détecter les anti-MOG Abs chez les patients atteints d'un trouble associé aux anticorps anti-glycoprotéine oligodendrocytaire de NMOSD/myéline. Les tests CSF pour MOG ou AQP-4 Abs ne sont pas habituellement conseillé. Il n'offre pas d'avantages supplémentaires pour faciliter le diagnostic MOG-EM ou NMOSD.
Asunto(s)
Autoanticuerpos , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Femenino , Adulto , Masculino , Técnica del Anticuerpo Fluorescente Indirecta/métodos , Acuaporina 4/inmunología , Persona de Mediana Edad , Imagen por Resonancia Magnética/métodos , Inmunosupresores/uso terapéuticoRESUMEN
BACKGROUND: The previous Japanese clinical practice guidelines for multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) were published in 2017. Recently, for the first time in 6 years, the MS and NMOSD guideline development committee revised the Japanese guidelines for MS, NMOSD, and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). METHODS: The committee utilized the Grading of Recommendations Assessment, Development, and Evaluation system based on the "Minds Handbook for Clinical Practice Guideline Development 2020 Ver. 3.0â³ with a focus on clinical questions (CQs). The committee also discussed clinical issues other than CQs, categorizing them as a question-and-answer (Q&A) section, including "issues on which experts' opinions agree to a certain extent" and "issues that are important but not included in the CQ". RESULTS: The committee identified 3, 1, and 1 key CQs related to MS, NMOSD, and MOGAD, respectively, and presented recommendations. A Q&A session regarding disease-modifying therapies and relapse prevention therapies for MS, NMOSD, and MOGAD was conducted. The revised guidelines were published in September 2023. CONCLUSIONS: The Japanese guidelines for clinical practice on MS, NMOSD, and MOGAD were updated. Treatment strategies for MS, NMOSD, and MOGAD are changing, and these updated guidelines may assist with treatment decisions for these diseases in clinical practice.
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Esclerosis Múltiple , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/terapia , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/tratamiento farmacológico , Glicoproteína Mielina-Oligodendrócito/inmunología , Esclerosis Múltiple/terapia , Esclerosis Múltiple/inmunología , Esclerosis Múltiple/diagnóstico , Japón , Guías de Práctica Clínica como Asunto/normas , Autoanticuerpos/sangreRESUMEN
Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated primary inflammatory myelinopathy of the central nervous system that primarily affects the optic nerve and spinal cord. The aquaporin 4 antibody (AQP4-Ab) is a specific autoantibody marker for NMOSD. Most patients with NMOSD are seropositive for AQP4-Ab, thus aiding physicians in identifying ways to treat NMOSD. AQP4-Ab has been tested in many clinical and laboratory studies, demonstrating effectiveness in diagnosing NMOSD. Recently, novel assays have been developed for the rapid and accurate detection of AQP4-Ab, providing further guidance for the diagnosis and treatment of NMOSD. This article summarizes the importance of rapid and accurate diagnosis for treating NMOSD based on a review of the latest relevant literature. We discussed current challenges and methods for improvement to offer new ideas for exploring rapid and accurate AQP4-Ab detection methods, aiming for early diagnosis of NMOSD.
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Acuaporina 4 , Autoanticuerpos , Diagnóstico Precoz , Neuromielitis Óptica , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/sangre , Humanos , Acuaporina 4/inmunología , Autoanticuerpos/sangre , Biomarcadores/sangreRESUMEN
Rare demyelinating diseases are a group of diseases whose pathogenesis is based on the process of demyelination. This group of diseases includes acute multiple encephalomyelitis (ADEM), opticoneuromyelitis spectrum diseases (NMOSD) and anti-myelin-oligodendrocyte glycoprotein-associated diseases (MOG-antibodies-associated diseases - MOGAD). Recently, new biological drugs for pathogenetic therapy have been developed, which have shown their effectiveness and good tolerability in comparison with therapy with first- and second-line drugs. Aim of the study - analysis of modern possibilities of pathogenetic treatment of patients with ADEM, seronegative and seropositive patients with NMOSD. The analysis was carried out on the basis of English-language publications in PubMed published over the past five years. This review summarizes current ideas about the possibilities of pathogenetic treatment of rare diseases. The advantages of using ravulizumab over other representatives of a new biological therapy associated with the use of monoclonal antibodies are shown. The analyzed data allow us to conclude that there is a significant development of pathogenetic treatment options for ZSONM. However, the effectiveness of new therapeutic biological drugs is still limited due to the lack of a large amount of clinical data to confirm, which creates the need to continue analyzing the experience of their use.
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Enfermedades Raras , Humanos , Enfermedades Raras/tratamiento farmacológico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Neuromielitis Óptica/tratamiento farmacológico , Neuromielitis Óptica/inmunología , Glicoproteína Mielina-Oligodendrócito/inmunología , Enfermedades Desmielinizantes/tratamiento farmacológicoRESUMEN
OBJECTIVE: To compare the diagnostic criteria of 2006 (DC 2006) and 2015 (DC 2015) in the Russian population of patients with suspected neuromyelitis optica spectrum disorders (NMOSD), with the calculation of their sensitivity, specificity, accuracy and predictive value. MATERIAL AND METHODS: We reviewed medical records of suspected NMOSD patients who were therefore examined for the presence of serum autoantibodies targeting the aquaporin-4 water channel protein (AQP4-IgG) in 6 specialized Russian (Nizhny Novgorod and Moscow) medical centers. One hundred patients (78 female), aged 17 to 74 years (mean 38.1±13.3 years), were included. The follow-up period ranged from 4 to 108 months (mean 59.7±31.6 months). RESULTS: During the follow-up the diagnosis of NMOSD was confirmed in 32 people, and 68 patients had diagnoses different from NMOSD. At the disease onset, 68.8% of patients were seropositive for AQP4-IgG. The mean time for confirming NMOSD diagnosis was 15.2±14.2 months. At the disease onset, 36% of patients fulfilled the DC 2015, the diagnosis was subsequently confirmed in 77.8% out of them. 26% of the patients fulfilled the DC 2006, the diagnosis was subsequently confirmed in 84.6% out of them. The sensitivity of DC 2006/DC 2015 was 69%/88%, specificity 94%/88%, accuracy 86%/88%, negative predictive value 85%/94%, positive predictive value 86%/78%. CONCLUSION: The specificity, sensitivity and accuracy of modern diagnostic criteria for NMOSD In Russian patients is comparable to those obtained in foreign studies. DC 2015 helps to diagnose NMOSD earlier than DC 2006, but they have a lower specificity.
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Acuaporina 4 , Autoanticuerpos , Neuromielitis Óptica , Sensibilidad y Especificidad , Humanos , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/sangre , Neuromielitis Óptica/inmunología , Adulto , Femenino , Persona de Mediana Edad , Masculino , Federación de Rusia , Autoanticuerpos/sangre , Anciano , Adolescente , Acuaporina 4/inmunología , Adulto Joven , Inmunoglobulina G/sangre , Valor Predictivo de las PruebasRESUMEN
OBJECTIVE: Autoimmune neurologic disorders encompass a broad category of diseases characterized by immune system attack of the central, peripheral, or autonomic nervous systems. This article provides information on both acute and maintenance immunotherapy used to treat autoimmune neurologic disorders as well as a review of symptomatic management and special considerations when caring for patients with these diseases. LATEST DEVELOPMENTS: Over the past 20 years, more than 50 antibodies have been identified and associated with autoimmune neurologic disorders. Although advances in diagnostic testing have allowed for more rapid diagnosis, the therapeutic approach to these disorders has largely continued to rely on expert opinion, case series, and case reports. With US Food and Drug Administration (FDA) approval of biologic agents to treat neuromyelitis optica spectrum disorder (NMOSD) and myasthenia gravis as well as ongoing clinical trials for the treatment of autoimmune encephalitis, the landscape of immunotherapy options continues to expand. Consideration of the unique pathogenesis of individual autoimmune neurologic disorders as well as the mechanism of action of the diverse range of treatment options can help guide treatment decisions today while evidence from clinical trials informs new therapeutics in the future. ESSENTIAL POINTS: Recognizing patients who have a clinical history and examination findings concerning for autoimmune neurologic disorders and conducting a thorough and directed imaging and laboratory evaluation aimed at ruling out mimics, identifying specific autoimmune syndromes, and screening for factors that may have an impact on immunotherapy choices early in the clinical course are essential to providing optimal care for these patients. Providers must consider immunotherapy, symptomatic treatment, and a multidisciplinary approach that addresses each patient's unique needs when treating patients with autoimmune neurologic disorders.
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Enfermedades Autoinmunes del Sistema Nervioso , Humanos , Enfermedades Autoinmunes del Sistema Nervioso/diagnóstico , Enfermedades Autoinmunes del Sistema Nervioso/terapia , Enfermedades Autoinmunes del Sistema Nervioso/inmunología , Enfermedades Autoinmunes del Sistema Nervioso/fisiopatología , Inmunoterapia/métodos , Femenino , Masculino , Neuromielitis Óptica/terapia , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/inmunología , Enfermedades del Sistema Nervioso/terapia , Enfermedades del Sistema Nervioso/diagnóstico , Persona de Mediana Edad , AdultoRESUMEN
OBJECTIVE: This article reviews the clinical features, MRI characteristics, diagnosis, and treatment of aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). The main differences between these disorders and multiple sclerosis (MS), the most common demyelinating disease of the central nervous system (CNS), are also highlighted. LATEST DEVELOPMENTS: The past 20 years have seen important advances in understanding rare demyelinating CNS disorders associated with AQP4 IgG and myelin oligodendrocyte glycoprotein (MOG) IgG. The rapidly expanding repertoire of immunosuppressive agents approved for the treatment of AQP4-NMOSD and emerging as potentially beneficial in MOGAD mandates prompt recognition of these diseases. Most of the recent literature has focused on the identification of clinical and MRI features that help distinguish these diseases from each other and MS, simultaneously highlighting major diagnostic pitfalls that may lead to misdiagnosis. An awareness of the limitations of currently available assays for AQP4 IgG and MOG IgG detection is fundamental for identifying rare false antibody positivity and avoiding inappropriate treatments. For this purpose, diagnostic criteria have been created to help the clinician interpret antibody testing results and recognize the clinical and MRI phenotypes associated with AQP4-NMOSD and MOGAD. ESSENTIAL POINTS: An awareness of the specific clinical and MRI features associated with AQP4-NMOSD and MOGAD and the limitations of currently available antibody testing assays is crucial for a correct diagnosis and differentiation from MS. The growing availability of effective treatment options will lead to personalized therapies and improved outcomes.
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Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/inmunología , Acuaporina 4/inmunología , Femenino , Autoanticuerpos/sangre , Masculino , Adulto , Imagen por Resonancia Magnética , Persona de Mediana EdadRESUMEN
OBJECTIVES: Cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infections in patients with Neuromyelitis optica spectrum disorder (NMOSD) remain unclear. The objective of this study was to investigate CMV and EBV infections in patients with NMOSD. METHODS: Serum immunoglobin (Ig) G antibodies against CMV and EBV were measured in patients with NMOSD and healthy controls (HCs), including anti-CMV, anti-EBV nuclear antigen-1 (EBNA-1), anti-EBV virus capsid antigen (VCA), and anti-EBV early antigen (EA) IgGs. The immune status ratio (ISR) was used to evaluate the serum anti-CMV and anti-EBV IgG levels and ISR â§1.10 was defined as seropositivity. RESULTS: In total, 238 serum samples were collected from 94 patients with NMOSD and 144 HCs, and no significant difference of sex and age between NMOSD and HCs. Comparing to the HCs, patients with NMOSD exhibited significantly higher serum anti-CMV IgG level. In contrast, the serum anti-EBNA1 IgG level was significantly lower in patients with NMOSD than in HCs. The serum anti-VCA and anti-EA IgG levels did not differ between the two groups, but the anti-EA seropositivity was significantly higher in NMOSD group than that in HC group. We did not find associations between serum anti-CMV or anti-EBV IgG levels and NMOSD disease stage, immunotherapy, or disability score. CONCLUSIONS: Our findings indicated that increased CMV infection and EBV recent infection, as well as reduced EBV latency infection were associated with the risk of NMOSD. Prospective cohort studies are needed to verify our findings and clarify the correlation between CMV and EBV infections and clinical characteristics of NMOSD.
Asunto(s)
Anticuerpos Antivirales , Infecciones por Citomegalovirus , Infecciones por Virus de Epstein-Barr , Inmunoglobulina G , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/sangre , Neuromielitis Óptica/inmunología , Femenino , Masculino , Infecciones por Virus de Epstein-Barr/complicaciones , Infecciones por Virus de Epstein-Barr/inmunología , Infecciones por Virus de Epstein-Barr/sangre , Adulto , Persona de Mediana Edad , Infecciones por Citomegalovirus/inmunología , Infecciones por Citomegalovirus/complicaciones , Infecciones por Citomegalovirus/sangre , Anticuerpos Antivirales/sangre , Inmunoglobulina G/sangre , Herpesvirus Humano 4/inmunología , Antígenos Nucleares del Virus de Epstein-Barr/inmunología , Antígenos Nucleares del Virus de Epstein-Barr/sangre , Anciano , Adulto JovenRESUMEN
BACKGROUND: Psychiatric comorbidities are common in Multiple Sclerosis (MS) and are increasingly recognised in Aquaporin-4-Antibody Neuromyelitis Optica Spectrum Disorders (AQP4-Ab NMOSD) and Myelin Oligodendrocyte Glycoprotein-Antibody Associated Disease (MOGAD). However, it is unclear if these psychiatric comorbidities predate neurological diagnosis or classical neurological symptoms that are conventionally used to establish the onset of these central nervous system inflammatory demyelinating diseases. We sought to: (1) assess the frequency and incidence of psychiatrist-diagnosed psychiatric disorders before and after formal MS, AQP4-Ab NMOSD, and MOGAD diagnosis, and (2) identify potential factors associated with the presence of pre-existing psychiatric morbidity and depression severity at the first clinical visit for MS patients. METHODS: A retrospective observational study was performed on MS, AQP4-Ab NMOSD, and MOGAD patients seen at the National Neuroscience Institute (NNI) Singapore. Individuals with psychiatrist-diagnosed psychiatric disorders before and after neurological diagnosis were identified. Demographic, clinical data, and Patient Health Questionnaire (PHQ)-9 score at first clinic visit were collected and analysed. RESULTS: Three hundred and ninety-nine patients (249 MS, 102 AQP4-Ab NMOSD, 48 MOGAD) were included. A higher proportion of MS patients (13/249, 5.2%) had psychiatric disorders before neurological diagnosis, compared to AQP4-Ab NMOSD (1/102, 1.0%) and MOGAD (0/48, 0.0%) (p = 0.054). Within MS patients, univariate logistic regression revealed that age, sex, race, MS subtype, initial MRI lesion load, and interval between classical MS symptom onset to MS diagnosis were not associated with pre-existing psychiatric disorders. Mean PHQ-9 score for MS patients at their first MS consult was 4.4 (cut-off for no/minimal depression is ≤4); no clinical factors were predictive of higher PHQ-9 scores on univariate linear regression. The proportion of MS patients (29/236, 12.2%) who developed psychiatric illness after neurological diagnosis was not different from AQP4-Ab NMOSD (9/101, 8.9%) (p > 0.999), while this was significantly higher compared to MOGAD (0/48, 0.0%) (p = 0.021). The incidence rate of psychiatric diseases after neurological diagnosis, accounting for follow up time, was also similar between MS and AQP4-Ab NMOSD (incidence rate ratio 1.2; 95% confidence interval 0.54 - 2.8; p = 0.689). CONCLUSION: There is a significant psychiatric burden prior to MS diagnosis compared to AQP4-Ab NMOSD and MOGAD. The increased frequency of psychiatric comorbidity after NMOSD diagnosis merits further study to investigate the determinants of this phenomenon.
Asunto(s)
Acuaporina 4 , Autoanticuerpos , Esclerosis Múltiple , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica , Humanos , Femenino , Masculino , Acuaporina 4/inmunología , Neuromielitis Óptica/epidemiología , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/diagnóstico , Adulto , Estudios Retrospectivos , Esclerosis Múltiple/epidemiología , Esclerosis Múltiple/diagnóstico , Persona de Mediana Edad , Glicoproteína Mielina-Oligodendrócito/inmunología , Autoanticuerpos/sangre , Trastornos Mentales/epidemiología , Trastornos Mentales/diagnóstico , Comorbilidad , Enfermedades Autoinmunes Desmielinizantes SNC/inmunología , Enfermedades Autoinmunes Desmielinizantes SNC/epidemiología , Enfermedades Autoinmunes Desmielinizantes SNC/diagnóstico , Enfermedades Autoinmunes Desmielinizantes SNC/sangreRESUMEN
Neuromyelitis optica spectrum of disorders is a rare cause of optic neuritis in children. It is a critical diagnosis requiring urgent management, with delays carrying both life- and sight-threatening complications. Most of the published literature on this entity is in adult patients, with only a few case reports to guide management in the paediatric population. The purpose of this article is to shareour experience in the management of this condition in a child, and thus hopefully add to the limited body of knowledge currently available.
Asunto(s)
Acuaporina 4 , Biomarcadores , Gastroenteritis , Inmunoglobulina G , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/sangre , Acuaporina 4/inmunología , Gastroenteritis/complicaciones , Gastroenteritis/diagnóstico , Inmunoglobulina G/sangre , Biomarcadores/sangre , Femenino , Niño , Enfermedad Aguda , Imagen por Resonancia Magnética , Neuritis Óptica/diagnóstico , Neuritis Óptica/inmunología , Ceguera/etiología , MasculinoRESUMEN
BACKGROUND: Aquaporin-4 (AQP4) antibody-associated neuromyelitis optica spectrum disorder (NMOSD) is an antibody-mediated inflammatory disease of the central nervous system. We have undertaken a systematic review and meta-analysis to ascertain the sex ratio and mean age of onset for AQP4 antibody associated NMOSD. We have also explored factors that impact on these demographic data. METHODS: A systematic search of databases was conducted according to the PRISMA guidelines. Articles reporting sex distribution and age of onset for AQP4 antibody-associated NMSOD were reviewed. An initially inclusive approach involving exploration with regression meta-analysis was followed by an analysis of just AQP4 antibody positive cases. RESULTS: A total of 528 articles were screened to yield 89 articles covering 19,415 individuals from 88 population samples. The female:male sex ratio was significantly influenced by the proportion of AQP4 antibody positive cases in the samples studied (p < 0.001). For AQP4 antibody-positive cases the overall estimate of the sex ratio was 8.89 (95% CI 7.78-10.15). For paediatric populations the estimate was 5.68 (95% CI 4.01-8.03) and for late-onset cases, it was 5.48 (95% CI 4.10-7.33). The mean age of onset was significantly associated with the mean life expectancy of the population sampled (p < 0.001). The mean age of onset for AQP4 antibody-positive cases in long-lived populations was 41.7 years versus 33.3 years in the remainder. CONCLUSIONS: The female:male sex ratio and the mean age of onset of AQP4 antibody-associated NMOSD are significantly higher than MS. The sex ratio increases with the proportion of cases that are positive for AQP4 antibodies and the mean age of onset increases with population life expectancy.
Asunto(s)
Edad de Inicio , Acuaporina 4 , Autoanticuerpos , Neuromielitis Óptica , Humanos , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/sangre , Acuaporina 4/inmunología , Femenino , Masculino , Autoanticuerpos/sangre , Razón de MasculinidadRESUMEN
Neuromyelitis optica spectrum disorder (NMOSD) is a clinical syndrome characterized by attacks of acute optic neuritis and transverse myelitis. We report a case with paraneoplastic NMOSD that improved after immunosuppressive therapy, surgical resection, and chemotherapy. A 48-year-old woman initially presented with gradual binocular visual loss over the course of one week. The patient was evaluated using magnetic resonance imaging (MRI), computed tomography (CT), visual evoked potential (VEP), pathological biopsy, immunohistochemistry, and autoimmune antibody testing. The brain MRI findings were normal. The VEP revealed prolonged P100 latencies in the right eye and an absence of significant waves in the left eye. Positive serum AQP4-IgG antibodies were found. The patient was diagnosed as NMOSD. Then the patient responded well to treatment with methylprednisolone. An ovarian tumor was found in the patient using abdominal MRI and CT. The tumor was surgically resected, and a pathological biopsy revealed that it was ovarian dysgerminoma. The patient received four rounds of chemotherapy after surgery. One month after the final chemotherapy treatment, a positron emission tomography (PET) scan revealed no tumor. The vision of the patient gradually recovered and serum AQP4 was negative. Furthermore, we summarized the characteristics of patients diagnosed with paraneoplastic NMOSD associated with ovarian neoplasms in previous studies. This is a characteristic case of overlapping NMOSD and ovarian dysgerminoma, demonstrating the importance of tumor therapy in cases of paraneoplastic NMOSD.
Asunto(s)
Neuromielitis Óptica , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/complicaciones , Neoplasias Ováricas/diagnóstico , Persona de Mediana Edad , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/inmunología , Neuromielitis Óptica/etiología , Neuromielitis Óptica/complicaciones , Acuaporina 4/inmunología , Disgerminoma/diagnóstico , Disgerminoma/complicaciones , Disgerminoma/patología , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Imagen por Resonancia MagnéticaRESUMEN
Background: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease affecting the central nervous system (CNS). NMOSD pathogenesis involves systemic inflammation. However, a causal relationship between circulating cytokine levels and NMOSD remains unclear. Methods: Mendelian randomization (MR) approaches were used to investigate the potential association between genetically determined circulating 19 inflammatory cytokines and 12 chemokines levels and the risk of developing NMOSD. Results: After Bonferroni correction, the risk of aquaporin 4-antibody (AQP4-ab)-positive NMOSD was suggested to be causally associated with the circulating levels of three cytokines, including interleukin (IL)-4 [odds ratio (OR): 11.01, 95% confidence interval (CI): 1.16-104.56, P = 0.037], IL-24 (OR: 161.37; 95% CI: 2.46-10569.21, P = 0.017), and C-C motif chemokine 19 (CCL19) (OR: 6.87, 95% CI: 1.78-26.93, P = 0.006). Conclusion: These findings suggest that a genetic predisposition to higher levels of IL-4, IL-24, and CCL19 may exert a causal effect on the risk of AQP4-ab-positive NMOSD. Further studies are warranted to clarify how these cytokines affect the development of AQP4-ab-positive NMOSD.
Asunto(s)
Citocinas , Predisposición Genética a la Enfermedad , Análisis de la Aleatorización Mendeliana , Neuromielitis Óptica , Neuromielitis Óptica/sangre , Neuromielitis Óptica/genética , Neuromielitis Óptica/inmunología , Humanos , Citocinas/sangre , Acuaporina 4/inmunología , Acuaporina 4/genética , Polimorfismo de Nucleótido Simple , Factores de Riesgo , Autoanticuerpos/sangre , Autoanticuerpos/inmunologíaRESUMEN
The treatment of primary Sjögren's syndrome (pSS) coexisting with neuromyelitis optica spectrum disorder (NMOSD) using protein-A immunoadsorption combined with immunosuppressive therapy has rarely been reported. Herein, we present the case of a 35-year-old female diagnosed with pSS concomitant with NMOSD (pSS-NMOSD) who demonstrated a positive response to protein-A immunoadsorption after failing to respond to therapy comprising high-dose intravenous methylprednisolone (IVMP) and intravenous immunoglobulin (IVIG). Within one week of receiving three sessions of immunoadsorption combined with immunosuppressive treatment, the patient's clinical symptoms (blurred vision, paraparesis, and dysfunctional proprioception) significantly improved. Additionally, a rapid decrease in the circulating levels of Aquaporin-4 immunoglobulin G antibodies (AQP4-IgG), immunoglobulin (Ig) A, IgG, IgM, erythrocyte sedimentation rate (ESR), and rheumatoid factor (RF) were observed. Magnetic resonance imaging (MRI) further revealed a significant reduction in the lesions associated with longitudinal extensive transverse myelitis. During the follow-up period, prednisolone was gradually tapered to a maintenance dose of 5-10 mg/day, whereas mycophenolate mofetil (MMF) was maintained at 1.0-1.5 g/day. The patient's condition has remained stable for four years, with no signs of recurrence or progression observed on imaging examination. Therefore, this case suggests that protein A immunoadsorption may represent a potentially effective therapeutic option for patients with pSS-NMOSD who are refractory to conventional treatments.