RESUMO
BACKGROUND AND OBJECTIVES: Attack prevention is crucial in managing neuromyelitis optica spectrum disorders (NMOSDs). Eculizumab (ECU), an inhibitor of the terminal complement cascade, was highly effective in preventing attacks in a phase III trial of aquaporin-4 (AQP4)-IgG seropositive(+) NMOSDs. In this article, we evaluated effectiveness and safety of ECU in routine clinical care. METHODS: We retrospectively evaluated patients with AQP4-IgG+ NMOSD treated with ECU between December 2014 and April 2022 at 20 German and 1 Austrian university center(s) of the Neuromyelitis Optica Study Group (NEMOS) by chart review. Primary outcomes were effectiveness (assessed using annualized attack rate [AAR], MRI activity, and disability changes [Expanded Disability Status Scale {EDSS}]) and safety (including adverse events, mortality, and attacks after meningococcal vaccinations), analyzed by descriptive statistics. RESULTS: Fifty-two patients (87% female, age 55.0 ± 16.3 years) received ECU for 16.2 (interquartile range [IQR] 9.6 - 21.7) months. Forty-five patients (87%) received meningococcal vaccination before starting ECU, 9 with concomitant oral prednisone and 36 without. Seven of the latter (19%) experienced attacks shortly after vaccination (median: 9 days, IQR 6-10 days). No postvaccinal attack occurred in the 9 patients vaccinated while on oral prednisone before starting ECU and in 25 (re-)vaccinated while on ECU. During ECU therapy, 88% of patients were attack-free. The median AAR decreased from 1.0 (range 0-4) in the 2 years preceding ECU to 0 (range 0-0.8; p < 0.001). The EDSS score from start to the last follow-up was stable (median 6.0), and the proportion of patients with new T2-enhancing or gadolinium-enhancing MRI lesions in the brain and spinal cord decreased. Seven patients (13%) experienced serious infections. Five patients (10%; median age 53.7 years) died on ECU treatment (1 from myocardial infarction, 1 from ileus with secondary sepsis, and 3 from systemic infection, including 1 meningococcal sepsis), 4 were older than 60 years and severely disabled at ECU treatment start (EDSS score ≥ 7). The overall discontinuation rate was 19%. DISCUSSION: Eculizumab proved to be effective in preventing NMOSD attacks. An increased risk of attacks after meningococcal vaccination before ECU start and potentially fatal systemic infections during ECU-particularly in patients with comorbidities-must be considered. Further research is necessary to explore optimal timing for meningococcal vaccinations. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that eculizumab reduces annualized attack rates and new MRI lesions in AQP4-IgG+ patients with NMOSD.
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Anticorpos Monoclonais Humanizados , Neuromielite Óptica , Humanos , Neuromielite Óptica/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Masculino , Anticorpos Monoclonais Humanizados/uso terapêutico , Adulto , Estudos Retrospectivos , Idoso , Inativadores do Complemento/uso terapêutico , Resultado do Tratamento , Estudos de Coortes , Vacinas Meningocócicas , Aquaporina 4/imunologia , Imageamento por Ressonância MagnéticaAssuntos
Anticorpos Monoclonais Humanizados , Aquaporina 4 , Imunoglobulina G , Vacinas Meningocócicas , Neuromielite Óptica , Humanos , Aquaporina 4/imunologia , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/imunologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Feminino , Adulto , MasculinoRESUMO
OBJECTIVE: The clinical symptoms of neuromyelitis optica spectrum disorder (NMOSD) and acute cervical spondylotic myelopathy (CSM) may overlap in some cases. This study aimed to investigate the differences in imaging features between NMOSD and CSM in acute myelopathy. METHODS: We included 78 patients in this retrospective study, including 28 NMOSD patients and 50 CSM patients. The demographic characteristics and clinical symptoms of the two groups of patients were compared. The T1 signal intensity, length of the spinal cord involved by T2 hyperintensity, degree of intervertebral disc degeneration, proportion of thoracic and lumbar cord involvement, proportion of brain involvement and lesion enhancement rate in magnetic resonance imaging (MRI) were compared between the two groups of patients. The number, length, location on the sagittal image, pattern on the sagittal image, and distribution on the axial image of the lesions in the contrast-enhanced MRI of the two groups were evaluated. RESULTS: There were differences between NMOSD and CSM patients in the proportion of women, the proportion of bowel and bladder symptoms, mRS levels, the length of the spinal cord involved by T2 hyperintensity, degree of intervertebral disc degeneration, the proportion of thoracic and lumbar cord involvement, the proportion of brain involvement, the enhancement rate and number of lesions (p < 0.05). Among NMOSD patients, linear, patchy and ring or semi-ring enhancement were present in 8(30.8%) ,14 (53.8%) and 4(15.4%)patients, respectively, and axial gray and white matter were involved in 17 (65.4%) patients. Among patients with CSM, 9(36.0%) patients showed longitudinal oriented flake, 16 (64.0%) patients showed pancake-like enhancement, and 21 (84.0%) patients showed axial white matter involvement only. The differences in enhancement pattern on sagittal images and axial involvement were statistically significant (p < 0.05). CONCLUSIONS: Early differential diagnosis of NMOSD and CSM in acute myelopathy can be made by analyzing images and the number, length, sagittal enhancement pattern, and axial involvement of gadolinium-enhanced lesions.
Assuntos
Imageamento por Ressonância Magnética , Neuroimagem , Neuromielite Óptica , Espondilose , Humanos , Feminino , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Espondilose/diagnóstico por imagem , Espondilose/complicações , Imageamento por Ressonância Magnética/métodos , Neuroimagem/métodos , Doenças da Medula Espinal/diagnóstico por imagem , Doenças da Medula Espinal/patologia , Idoso , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologiaRESUMO
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.
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Neuromielite Óptica , Humanos , Neuromielite Óptica/imunologia , Neuromielite Óptica/epidemiologia , Feminino , Adulto , Masculino , Estudos Transversais , Estudos Retrospectivos , Pessoa de Meia-Idade , Aquaporina 4/imunologia , Adulto Jovem , Autoanticorpos/sangueRESUMO
BACKGROUND: Prodromal phases are well recognized in many inflammatory and neurodegenerative diseases, including multiple sclerosis. We evaluated the possibility of a prodrome in aquaporin-4 antibody positive (AQP4+) neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD) using health administrative data. METHODS: We investigated individuals with AQP4 + NMOSD and MOGAD, confirmed by medical chart review, in Ontario, Canada. Each NMOSD and MOGAD participant was matched 1:5 to general population controls by sex, birth year, immigrant status, and region. Total outpatient visits and hospitalizations were compared in the 5 years preceding the incident attack in multivariable negative binomial models. RESULTS: We identified 96 people with AQP4 + NMOSD, matched to 479 controls, and 61 people with MOGAD, matched to 303 controls. In the 5 years preceding the incident attack, health care use was elevated for outpatient visits and hospitalizations for the NMOSD cohort (adjusted rate ratio (aRR): 1.47; 95% confidence interval (CI): 1.25-1.73; aRR: 1.67; 95% CI: 1.19-2.36, respectively) but not for MOGAD. Rate ratios steadily increased in NMOSD for outpatient visits in the 2 years preceding the incident attack. CONCLUSION: Our findings support a prodromal phase preceding clinical onset of AQP4 + NMOSD. Earlier recognition and management of NMOSD patients may be possible.
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Aquaporina 4 , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Sintomas Prodrômicos , Humanos , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/terapia , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Aquaporina 4/imunologia , Hospitalização/estatística & dados numéricos , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Ontário/epidemiologia , Autoanticorpos/sangue , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/imunologia , Doenças Autoimunes Desmielinizantes do Sistema Nervoso Central/epidemiologiaRESUMO
Demyelinating disorders of the nervous system constitute a broad spectrum of neurological conditions characterized by the depletion of myelin sheaths accompanied by inflammatory cell infiltration, manifesting in either the central or peripheral nervous system. The former primarily encompasses conditions such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD), while the latter is exemplified predominantly by Guillain-Barre syndrome (GBS). Recent investigations have revealed that dyslipidemia may be related to the occurrence and development of neurological demyelination, but there are fewer analyses and summaries of related advances in China. Consequently, this review aims to comprehensively outline advancements in research concerning the correlation between dyslipidemia and neurological demyelinating disordersand discusses in depth the interrelationship between dyslipidemia and neurological demyelinating diseases, so as to provide reference for the prevention and treatment of neurological demyelinating diseases.
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Doenças Desmielinizantes , Dislipidemias , Neuromielite Óptica , Humanos , Esclerose Múltipla , Síndrome de Guillain-BarréRESUMO
A 32-year-old lady presented with acute paroxysmal facial pain in the V1-V2 distribution, lower cranial nerve dysfunction, and mild long-tract neurological signs. Paroxysmal facial pain with features of trigeminal autonomic cephalgia (TAC) and trigeminal neuralgia (TN) (Tic) was the unique presentation in this case, explained by involvement of the somatotopically arranged spinal trigeminal nucleus. She had two attacks of area postrema syndrome (APS) preceding the current symptoms, evaluated as a gastroenterological disorder, causing a delay in imaging and AQP4-seropositive diagnosis of neuromyelitis optica spectrum disorder (NMOSD). She recovered from brainstem symptoms with immunosuppression but continued to have painful tonic spasms and neuropathic pain as immediate sequelae. The untreated first attack, AQP4 positivity, and relapse within the 1st year are all risk factors for further relapses and long-term morbidity, as was the case with our patient.
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Neuromielite Óptica , Cefalalgias Autonômicas do Trigêmeo , Neuralgia do Trigêmeo , Humanos , Feminino , Adulto , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/complicações , Neuralgia do Trigêmeo/etiologia , Neuralgia do Trigêmeo/diagnóstico , Cefalalgias Autonômicas do Trigêmeo/diagnóstico , Cefalalgias Autonômicas do Trigêmeo/etiologiaRESUMO
Acquired demyelinating syndromes (ADS) represent acute neurologic illnesses characterized by deficits persisting for at least 24hours and involving the optic nerve, brain, or spinal cord, associated with regional areas of increased signal on T2-weighted images. In children, ADS may occur as a monophasic illness or as a relapsing condition, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Almost all young people with MS have a relapsing-remitting course with clinical relapses. Important strides have been made in delineating MS from other ADS subtypes. Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) and aquaporin 4-antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD) were once considered variants of MS; however, studies in the last decade have established that these are in fact distinct entities. Although there are clinical phenotypic overlaps between MOGAD, AQP4-NMOSD, and MS, cumulative biologic, clinical, and pathologic evidence allows discrimination between these conditions. There has been a rapid increase in the number of available disease-modifying therapies for MS and novel treatment strategies are starting to appear for both MOGAD and AQP4-NMOSD. Importantly, there are a number of both inflammatory and noninflammatory mimics of ADS in children with implications of management for these patients in terms of treatment.
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Leucoencefalopatias , Humanos , Criança , Leucoencefalopatias/patologia , Neuromielite Óptica/patologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Aquaporina 4/imunologiaRESUMO
Neuromyelitis optica (NMO) spectrum disorder (NMOSD) is a relapsing inflammatory disease of the CNS, characterized by the presence of serum aquaporin 4 (AQP4) autoantibodies (AQP4-IgGs) and core clinical manifestations such as optic neuritis, myelitis, and brain or brainstem syndromes. Some people exhibit clinical characteristics of NMOSD but test negative for AQP4-IgG, and a subset of these individuals are now recognized to have serum autoantibodies against myelin oligodendrocyte glycoprotein (MOG) - a condition termed MOG antibody-associated disease (MOGAD). Therefore, the concept of NMOSD is changing, with a disease spectrum emerging that includes AQP4-IgG-seropositive NMOSD, MOGAD and double-seronegative NMOSD. MOGAD shares features with NMOSD, including optic neuritis and myelitis, but has distinct pathophysiology, clinical profiles, neuroimaging findings (including acute disseminated encephalomyelitis and/or cortical encephalitis) and biomarkers. AQP4-IgG-seronegative NMOSD seems to be a heterogeneous condition and requires further study. MOGAD can manifest as either a monophasic or a relapsing disease, whereas NMOSD is usually relapsing. This Review summarizes the history and current concepts of NMOSD and MOGAD, comparing epidemiology, clinical features, neuroimaging, pathology and immunology. In addition, we discuss new monoclonal antibody therapies for AQP4-IgG-seropositive NMOSD that target complement, B cells or IL-6 receptors, which might be applied to MOGAD in the near future.
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Autoanticorpos , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Humanos , Neuromielite Óptica/imunologia , Neuromielite Óptica/diagnóstico , Glicoproteína Mielina-Oligodendrócito/imunologia , Autoanticorpos/imunologia , Autoanticorpos/sangue , Aquaporina 4/imunologiaRESUMO
INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a neuroinflammatory condition characterized by optic neuritis and transverse myelitis. While the current approach to NMOSD focuses on relapse-associated worsening (RAW), recent evidence indicates Relapse-Independent Disease Activity (RIDA) in patients. METHOD: Databases including Embase, PubMed, Scopus, and Web of Sciences were systematically searched up to December 2023. No restrictions were applied. Inclusion criteria focused on studies reporting evidence of RIDA in NMOSD patients. Data extraction involved details such as study title, author, participant characteristics, treatment, evaluation methods, positive findings according to RIDA, and prevalence of findings in NMOSD patients. This study is conducted following the PRISMA guidelines with a registered protocol on PROSPERO (ID = CRD42023492352). RESULT: Of 802 studies, 38 were included in the systematic review, covering 1881 NMOSD patients. AQP4-IGg status was positive in 90.6 % of the patients. Ocular findings indicative of RIDA were reported in 23 studies, including thinning of GCIPL, RNFL, GCC, and GCL layers, foveal and macular shape and volume abnormalities, vessel loss, and visual evoked potentials (VEPs) abnormalities. MRI findings supporting the RIDA were reported in 13 studies, including new lesion incidence and brain and spinal cord atrophy. Serum and CSF RIDA-supporting findings were reported in five studies, including elevation in sGFAP and sNFL. Biopsies and autopsies suggested inflammatory processes in relapse-free patients in 2 studies. The predominant manifestation of RIDA in NMOSD was identified in the visual system, suggesting the impaired retinal glial cells like Müller cells during the relapse-free period in NMOSD. INTERPRETATION: Our systematic review provides valuable insights into RIDA in NMOSD. Establishing guidelines for the diagnosis and treatment of RIDA is crucial. Further studies are needed to provide robust evidence on RIDA in NMOSD patients.
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Neuromielite Óptica , Humanos , Progressão da Doença , Neuromielite Óptica/fisiopatologia , Neuromielite Óptica/diagnósticoRESUMO
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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Aquaporina 4 , Autoanticorpos , Diagnóstico Precoce , Neuromielite Óptica , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Neuromielite Óptica/sangue , Humanos , Aquaporina 4/imunologia , Autoanticorpos/sangue , Biomarcadores/sangueRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disorder characterized by inflammatory assaults on the central nervous system (CNS), particularly on the optic nerves and spinal cord. In recent years, a wider range of clinical manifestations of this complex disease have been observed, emphasizing the importance of gaining a more profound understanding beyond optic neuritis (ON) and transverse myelitis (TM). CURRENT KNOWLEDGE: This study explores the many clinical symptoms of NMOSD, including common and uncommon presentations. Distinctive aspects of ON, TM, and diencephalic/brainstem syndromes are examined, highlighting their unique characteristics in contrast to conditions such as multiple sclerosis. We also discuss extra-CNS involvement, such as unusual signs, including muscle involvement, retinal injury, auditory impairment, and rhinological symptoms. AIMS AND OBJECTIVES: Our study intends to highlight the wide range and complexity of NMOSD presentations, emphasizing the significance of identifying unusual symptoms for precise diagnosis and prompt management. The specific processes that contribute to the varied clinical presentation of NMOSD are not well understood despite existing information. This emphasizes the necessity for more study to clarify the mechanisms that cause different symptoms and discover new treatment targets for this complex autoimmune disorder. CONCLUSION: It is essential to acknowledge the complex and varied clinical manifestations of NMOSD to enhance diagnosis, treatment, and patient results. By enhancing our comprehension of the fundamental processes and investigating innovative therapeutic approaches, we may aim to enhance the quality of life for persons impacted by this illness.
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Neuromielite Óptica , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/fisiopatologia , HumanosRESUMO
BACKGROUND: Experimental studies have shown that repetitive trans-spinal magnetic stimulation (TsMS) decreases demyelination and enables recovery after spinal cord injury (SCI). However, the usefulness of TsMS in humans with SCI remains unclear. Therefore, the main objective of this study is to evaluate the effects of TsMS combined with kinesiotherapy on SCI symptoms. We describe a protocol treatment with TsMS and kinesiotherapy in a patient with SCI due to neuromyelitis optica (NMO)-associated transverse myelitis. CASE PRESENTATION: A 23-year-old white male with NMO spectrum disorders started symptoms in 2014 and included lumbar pain evolving into a mild loss of strength and sensitivity in both lower limbs. Five months later, the symptoms improved spontaneously, and there were no sensorimotor deficits. Two years later, in 2016, the symptoms recurred with a total loss of strength and sensitivity in both lower limbs. Initially, physiotherapy was provided in 15 sessions with goals of motor-sensory recovery and improving balance and functional mobility. Subsequently, TsMS (10 Hz, 600 pulses, 20-seconds inter-trains interval, at 90% of resting motor threshold of the paravertebral muscle) was applied at the 10th thoracic vertebral spinous process before physiotherapy in 12 sessions. Outcomes were assessed at three time points: prior to physiotherapy alone (T-1), before the first session of TsMS combined with kinesiotherapy (T0), and after 12 sessions of TsMS combined with kinesiotherapy (T1). The patient showed a 25% improvement in walking independence, a 125% improvement in balance, and an 18.8% improvement in functional mobility. The Patient Global Impression of Change Scale assessed the patient's global impression of change as 'much improved'. CONCLUSION: TsMS combined with kinesiotherapy may safely and effectively improve balance, walking independence, and functional mobility of patients with SCI due to NMO-associated transverse myelitis.
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Magnetoterapia , Neuromielite Óptica , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal , Humanos , Masculino , Neuromielite Óptica/terapia , Neuromielite Óptica/complicações , Adulto Jovem , Magnetoterapia/métodos , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/reabilitação , Traumatismos da Medula Espinal/terapia , Resultado do Tratamento , Terapia Combinada , Modalidades de FisioterapiaRESUMO
INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) and MOG-associated disease (MOGAD) are an increasingly recognized group of demyelinating disorders of the central nervous system. Previous studies suggest that prognosis is predicted by older age at onset, number of relapses, the severity of the first attack and autoantibody status. OBJECTIVE: To study prognostic factors associated with disability progression and additional relapses in the 3-year follow-up of a national NMOSD/MOGAD cohort. RESULTS: Out of 180 of the initial Portuguese cohort, data on 82 patients was available at the end of the follow-up period (2019-2022). Two patients died. Twenty (24.4%) patients had one or more attack in this period (25 attacks in total), mostly transverse myelitis (TM) (56.0%) or optic neuritis (32.0%). MOGAD was significantly associated with a monophasic disease course (p = 0.03), with milder attacks (p = 0.01), while AQP4 + NMOSD was associated with relapses (p = 0.03). The most common treatment modalities were azathioprine (38.8%) and rituximab (18.8%). AQP4 + NMOSD more frequently required chronic immunosuppressive treatment, particularly rituximab (p = 0.01). Eighteen (22.5%) had an EDSS ≥6 at the end of the follow-up. AQP4 + NMOSD (p < 0.01) and the occurrence of transverse myelitis (TM) during disease (p = 0.04) correlated with an EDSS≥6 at the end of the follow-up period. MOGAD was significantly associated with an EDSS<6 (p < 0.01), and MOG+ cases that reached an EDSS>6 were significantly older (64.0 ± 2.8 versus 31.0 ± 17.1, p = 0.017). A bivariate logistic regression model including the serostatus and TM attacks during disease history successfully predicted 72.2% of patients that progressed to an EDSS≥6. CONCLUSION: This study highlights that myelitis predict increased disability (EDSS≥6) in NMOSD/MOGAG and AQP4 positivity is associated with increased disability.
Assuntos
Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Sistema de Registros , Humanos , Neuromielite Óptica/epidemiologia , Feminino , Masculino , Portugal/epidemiologia , Adulto , Prognóstico , Pessoa de Meia-Idade , Glicoproteína Mielina-Oligodendrócito/imunologia , Estudos de Coortes , Progressão da Doença , Autoanticorpos/sangue , Pessoas com Deficiência , Avaliação da Deficiência , Aquaporina 4/imunologia , Adulto Jovem , Seguimentos , Idoso , RecidivaRESUMO
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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Esclerose Múltipla , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Humanos , Autoanticorpos/sangue , Japão , Esclerose Múltipla/terapia , Esclerose Múltipla/imunologia , Esclerose Múltipla/diagnóstico , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/imunologia , Neuromielite Óptica/terapia , Guias de Prática Clínica como AssuntoRESUMO
BACKGROUND: Little is known about the relationship between neighborhood disadvantage and neuromyelitis optica spectrum disorder (NMOSD) outcomes. OBJECTIVE: The objective is to determine the impact of neighborhood disadvantage on time from symptom onset to diagnosis and annualized relapse rate (ARR). METHODS: Neighborhood disadvantage were captured with the Area Deprivation Index (ADI), a validated measure of neighborhood-level disadvantage. Negative binomial regression models assessed the impact of ADI on diagnostic delay (⩾3 months between symptom onset and diagnosis) and ARR. RESULTS: A total of 158 NMOSD patients were identified, a majority of whom were White (56.3%) and female (89.9%) with a mean age of 46 years at diagnosis. The ADI did not significantly affect odds of diagnostic delay (odds ratio (OR) = 0.99, p = 0.26). In univariable models, the ADI was not significantly associated with ARR (OR = 1.004, p = 0.29), but non-White race (OR = 1.541, p = 0.02) and time on immunosuppressive therapies (ISTs; OR = 0.994, p = 0.03) were. White patients used IST for an average of 81% of the follow-up period, compared to an average of 65% for non-White patients (p < 0.01). CONCLUSION: No significant relationship between neighborhood-level disadvantage and diagnostic delay or ARR in NMOSD patients was observed. Non-White patients had a higher ARR, which may be related to less IST use.
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Neuromielite Óptica , Características de Residência , Humanos , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/etnologia , Neuromielite Óptica/diagnóstico , Feminino , Pessoa de Meia-Idade , Adulto , Masculino , Diagnóstico Tardio , Recidiva , População BrancaRESUMO
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.
Assuntos
Aquaporina 4 , Ativação do Complemento , Imunoglobulina G , Glicoproteína Mielina-Oligodendrócito , Neuromielite Óptica , Humanos , Neuromielite Óptica/líquido cefalorraquidiano , Neuromielite Óptica/imunologia , Neuromielite Óptica/sangue , Aquaporina 4/imunologia , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Glicoproteína Mielina-Oligodendrócito/imunologia , Imunoglobulina G/líquido cefalorraquidiano , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Autoanticorpos/líquido cefalorraquidiano , Autoanticorpos/sangue , Idoso , Complemento C5a/líquido cefalorraquidiano , Complemento C5a/metabolismo , Complemento C5a/imunologia , Adulto Jovem , Esclerose Múltipla/líquido cefalorraquidiano , Esclerose Múltipla/imunologia , Complemento C3a/metabolismo , Complemento C3a/líquido cefalorraquidiano , Complemento C3a/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/metabolismo , Complexo de Ataque à Membrana do Sistema Complemento/líquido cefalorraquidiano , Complexo de Ataque à Membrana do Sistema Complemento/imunologiaRESUMO
INTRODUCTION: Myelin oligodendrocyte glycoprotein-immunoglobulin G associated disease (MOGAD) is a clinical entity distinct from multiple sclerosis and aquaporin-4 (AQP4+)-IgG-positive neuromyelitis optica spectrum disorder. There is a lack of evidence regarding the efficacy and safety of current treatments used for MOGAD. AREAS COVERED: In this article, the authors review the currently available literature on the pharmacological management of MOGAD. This article is based on an extensive search for articles including meta-analyses, clinical trials, systematic reviews, observational studies, case series and case reports. EXPERT OPINION: Intravenous high-dose methylprednisolone is the most common therapy for acute attack with patients having a good treatment response. In cases with poor recovery, intravenous immunoglobulins (IVIG) or plasma-exchange proved to be effective. Maintenance therapies include mycophenolate mofetil, azathioprine, IVIG, oral corticosteroids, rituximab, and interleukin-6 receptor (IL6-R) antagonists. Rituximab is the most used drug while IL6-R antagonists emerged as an effective option for people not responding to current treatments. Larger prospective studies with longer follow-ups are needed to confirm whether the blockage of the IL6-R is an effective and safe option. Since there is no evidence of major safety issues related to the new available therapies, the authors believe that waiting for disease activity to consider a possible treatment change, is an unwise approach.
Assuntos
Glicoproteína Mielina-Oligodendrócito , Humanos , Glicoproteína Mielina-Oligodendrócito/imunologia , Imunoglobulina G/uso terapêutico , Imunoglobulinas Intravenosas/uso terapêutico , Imunoglobulinas Intravenosas/administração & dosagem , Metilprednisolona/uso terapêutico , Metilprednisolona/administração & dosagem , Neuromielite Óptica/tratamento farmacológicoRESUMO
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.
Assuntos
Modelos Animais de Doenças , Antígenos HLA , Camundongos Transgênicos , Animais , Camundongos , Humanos , Antígenos HLA/genética , Antígenos HLA/imunologia , Esclerose Múltipla/imunologia , Esclerose Múltipla/genética , Doenças Autoimunes/imunologia , Doenças Autoimunes/genética , Neuromielite Óptica/imunologia , Neuromielite Óptica/genética , Doenças do Sistema Nervoso Central/imunologia , Doenças do Sistema Nervoso Central/genéticaRESUMO
Neuromyelitis optica spectrum disorder (NMOSD), also known as Devic disease, is an autoimmune central nervous system disorder in humans that commonly causes inflammatory demyelination in the optic nerves and spinal cord. Inflammation in the optic nerves is termed optic neuritis (ON). ON is a common clinical presentation; however, it is not necessarily present in all NMOSD patients. ON in NMOSD can be relapsing and result in severe vision loss. To the best of our knowledge, no study utilises deep learning to classify ON changes on MRI among patients with NMOSD. Therefore, this study aims to deploy eight state-of-the-art CNN models (Inception-v3, Inception-ResNet-v2, ResNet-101, Xception, ShuffleNet, DenseNet-201, MobileNet-v2, and EfficientNet-B0) with transfer learning to classify NMOSD patients with and without chronic ON using optic nerve magnetic resonance imaging. This study also investigated the effects of data augmentation before and after dataset splitting on cropped and whole images. Both quantitative and qualitative assessments (with Grad-Cam) were used to evaluate the performances of the CNN models. The Inception-v3 was identified as the best CNN model for classifying ON among NMOSD patients, with accuracy of 99.5%, sensitivity of 98.9%, specificity of 93.0%, precision of 100%, NPV of 99.0%, and F1-score of 99.4%. This study also demonstrated that the application of augmentation after dataset splitting could avoid information leaking into the testing datasets, hence producing more realistic and reliable results.