RESUMO
BACKGROUND: Neuromyelitis Optica spectrum disorder (NMOSD) is an antibody-mediated autoimmune disease of the CNS, which especially affects the optic nerves and spinal cord. There is little known in Latin America (LATAM) about NMOSD, and few reports have been published in the literature so far. We aimed to describe an NMOSD study in a single center from Argentina. METHODS: A retrospective cross sectional study was carried out in a single reference center in the city of Buenos Aires, Argentina. Data were collected from January 2000 through December 2021 using medical records from patients attending Ramos Mejia Hospital in Buenos Aires, Argentina. Here we describe the clinical, laboratory, MRI, disability course, and treatment of 92 NMOSD patients. RESULTS: Mean age at the onset of symptoms was 31 years (range 2-68) with a female/male ratio of 4.8:1. 71.7 % had an early onset before the age of 50 years old, 8.7 % had a late onset of the disease and 19.6 % had an onset at pediatric age. The first symptom of NMOSD was optic neuritis in 47.8 % of the patients, followed by transverse myelitis, 33.7 % and area postrema syndrome, 5.4 %. 96.7 % of patients relapsed at least once during the follow-up period. The mean of the expanded disability status scale (EDSS) was 4.0 (range 2-8). 34,8 % had one or more associated autoimmune diseases. 78,6 % had a positive result for AQP4-IgG. The ratio of male to female was 1:8.4 vs.1:1.2 in the seropositive group vs. the seronegative. CSF results showed OCB type 2 in 6.3 %. The brain MRI did not show brain lesions in 71,7 % of the patients. 17 % presented spinal cord lesions with less than 3 vertebral segments. All patients received treatment with immunosuppressive drugs. Rituximab and azathioprine were the most used. CONCLUSIONS: This is the largest hospital-based study in an Argentina cross-sectional study of patients with NMOSD. Recurrent disease, early age at onset, female prevalence in AQP4-IgG+ patients, and the difficulty to assess new treatments, are the highlight features in our study of patients. Further Argentinian and LATAM studies will provide more information.
Assuntos
Neuromielite Óptica , Humanos , Masculino , Feminino , Criança , Pré-Escolar , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/epidemiologia , Neuromielite Óptica/complicações , Estudos Transversais , Estudos Retrospectivos , Aquaporina 4 , Argentina/epidemiologia , Imunoglobulina G , AutoanticorposRESUMO
Optic neuromyelitis (ONM), also called neuromyelitis optica spectrum (Neuromyelitis Optica Spectrum Disorders, NMOSD) is recognized as an inflammatory autoimmune demyelinating disease of the central nervous system, mediated by autoantibodies against the aquaporin-4 receptor (AQP4-IgG). It predominantly affects the optic nerves and the spinal cord.1-3 It is known that patients with immune disorders are more likely to present other autoimmune diseases, but the relation between juvenile idiopathic arthritis and ONM has not been completely described.5 In this paper, we report a case of a patient with juvenile idiopathic arthritis, presenting with a rapidly progressive neurological condition, who is treated with biological drugs.1-4
La neuromielitis óptica (NMO), también llamada espectro de la neuromielitis óptica (neuromyelitis optica spectrum disorders) se reconoce como una enfermedad inflamatoria, autoinmune, desmielinizante del sistema nervioso central, mediada por autoanticuerpos contra el receptor de acuaporina 4 (AQP4-IgG) que afecta predominantemente a los nervios ópticos y la médula espinal1-3. Es conocido que los pacientes con trastornos inmunitarios tienen más probabilidades de presentar otras enfermedades autoinmunes; sin embargo, no está completamente descrita la asociación entre artritis idiopática juvenil y NMO5. En este escrito se reporta el caso de una paciente que cursa con artritis idiopática juvenil, inició con compromiso neurológico rápidamente progresivo, y es tratada con medicamentos biológicos1-4.
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas , Artrite , Artrite Juvenil , Proteínas , Proteínas de Transporte , Aminoácidos, Peptídeos e ProteínasRESUMO
Here, a study of NMOSD in Central America and the Caribbean with a multinational collaborative, multicentric and descriptive approach involving 25 institutions from 9 countries is presented. Demographics, clinical manifestations, expanded disability scale status (EDSS), brain and spinal cord MRI, serological anti-AQP4-IgG and anti-MOG-IgG antibodies, and cerebrospinal fluid (CSF) oligoclonal bands were included. A central serological repository utilized the cell-based assay. The specimens outside of this network employed diverse methodologies. Data were collected at the Gorgas Commemorative Institute of Health Studies (ICGES), Panama, and included 186 subjects, of which 84% were females (sex ratio of 5.6:1). Mestizos constituted 72% of the study group. The median age was 42.5 years (IQR: 32.0-52.0). Associated autoimmune diseases (8.1%) were myasthenia gravis, Sjögren's syndrome and systemic lupus erythematosus. The most common manifestation was optic neuritis-transverse myelitis (42.5%). A relapsing course was described in 72.3% of cases. EDSS scores of 0-3.5 were reported in 57.2% of cases and higher than 7.0 in 14.5%. Positive anti-AQP4-IgG antibody occurred in 59.8% and anti-MOG-IgG antibody in 11.5% of individuals. Antibody testing was lacking for 13.4% of patients. The estimated crude prevalence of NMOSD from Panama and the Dominican Republic was 1.62/100,000 (incidence of 0.08-0.41) and 0.73/100,000 (incidence 0.02-0.14), respectively. This multinational study contributes additional insights and data on the understanding of NMOSD in this Latin American region.
RESUMO
Aquaporin-4 (AQP4) is the target of the specific immunoglobulin G autoantibody (AQP4-IgG) produced in patients with neuromyelitis optica spectrum disorders (NMOSD). Previous studies demonstrated that AQP4-IgG binding to astrocytic AQP4 leads to cell-destructive lesions. However, the early physiopathological events in Müller cells in the retina are poorly understood. Here, we investigated the consequences of AQP4-IgG binding to AQP4 of Müller cells, previous to the inflammatory response, on two of AQP4's key functions, cell volume regulation response (RVD) and cell proliferation, a process closely associated with changes in cell volume. Experiments were performed in a human retinal Müller cell line (MIO-M1) exposed to complement-inactivated sera from healthy volunteers or AQP4-IgG positive NMOSD patients. We evaluated AQP4 expression (immunofluorescence and western blot), water permeability coefficient, RVD, intracellular calcium levels and membrane potential changes during hypotonic shock (fluorescence videomicroscopy) and cell proliferation (cell count and BrdU incorporation). Our results showed that AQP4-IgG binding to AQP4 induces its partial internalization, leading to the decrease of the plasma membrane water permeability, a reduction of swelling-induced increase of intracellular calcium levels and the impairment of RVD in Müller cells. The loss of AQP4 from the plasma membrane induced by AQP4-IgG positive sera delayed Müller cells' proliferation rate. We propose that Müller cell dysfunction after AQP4 removal from the plasma membrane by AQP4-IgG binding could be a non-inflammatory mechanism of retinal injury in vivo, altering cell volume homeostasis and cell proliferation and consequently, contributing to the physiopathology of NMOSD.
Assuntos
Aquaporina 4/sangue , Membrana Celular/metabolismo , Células Ependimogliais/metabolismo , Imunoglobulina G/metabolismo , Neuromielite Óptica/sangue , Retina/metabolismo , Aquaporina 4/administração & dosagem , Biomarcadores/sangue , Linhagem Celular Transformada , Membrana Celular/patologia , Proliferação de Células/fisiologia , Tamanho Celular , Células Ependimogliais/patologia , Homeostase/fisiologia , Humanos , Imunoglobulina G/administração & dosagem , Neuromielite Óptica/patologia , Retina/lesões , Retina/patologiaRESUMO
BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is a complex disease characterized by a severe inflammation of the central nervous system (CNS). This disease typically manifests with recurrent optic neuritis (ON) and acute transverse myelitis (ATM). The clinical and radiological spectrum of NMOSD is little known in Latin America (LATAM) and few reports have been published in the literature so far. In Ecuador, no reports on NMOSD have been published. For this reason we aimed to assess the demographic, clinical and imaging characteristics of patients with NMOSD from third level hospitals from Ecuador. METHODS: This is a descriptive study in which we assessed medical reports of patients with inflammatory demyelinating diseases who were attended in third level hospitals from Ecuador in 2017. Then we applied the 2015 diagnostic criteria, those patients who met the new NMOSD diagnostic criteria were selected and analyzed. Additionally, exploratory sub-analyses were subsequently carried out. RESULTS: We identified 59 patients with NMOSD, the relative frequency of NMOSD was 15.9%. The multiple sclerosis (MS) /NMOSD ratio was 5.2:1. Twenty four percent of patients were newly defined as having NMOSD when 2015 criteria was applied. The median time to diagnoses was shorter by the 2015 criteria than 2006 criteria (p<0.001). NMOSD was more prevalent in women (female/male ratio 4.4:1). The disease onset was more frequent at the fourth decade of life. The most common symptoms at the disease onset were ON and the association of ON with ATM. The mean of expanded disability status scale (EDSS) was 4.8 (SD±1.8). Concomitant autoimmune diseases were infrequent in this population (11.9%). The brain magnetic resonance imaging (MRI) abnormalities were present in 25.7% of patients at disease onset. Spinal cord MRI showed longitudinally extensive transverse myelitis (LETM) in 91.5% of cases. Recurrent NMOSD was frequent in this cohort (88%). Positivity for antibodies against aquaporin-4 (AQP4-IgG) which was measured through indirect immunofluorescence assay (IIF) was identified in 81% of the patients tested. Patients with seronegative AQP4-IgG had higher grade of disability than seropositive patients (p<0.05). Ninety eight percent of patients received treatment with immunosuppressive drugs. Three patients died due to gastric cancer (1 patient) and infectious diseases (2 patients). CONCLUSIONS: This is the first descriptive study in an Ecuadorian cohort of patients with NMOSD. We show a wide epidemiological, clinical and radiological spectrum of NMOSD.
Assuntos
Mielite Transversa , Neuromielite Óptica , Aquaporina 4 , Autoanticorpos , Estudos de Coortes , Equador/epidemiologia , Feminino , Humanos , Masculino , Neuromielite Óptica/diagnóstico por imagem , Neuromielite Óptica/epidemiologiaRESUMO
BACKGROUND: A specific particularity of neurological diseases in Asia is the relative commonality of neuromyelitis optica (NMO) and Asian type MS (OSMS). Both conditions also occur in South American patients. The Brazilian population differs from the European and the Asian populations due to the mixture of ancestralities between European colonizers and African slaves. To better know the clinical characteristics of Brazilian patients with Asian type MS this study aimed to analyze the clinical, radiological and serological data that would help to distinguish between OSMS and NMO and clarify, in a Non-Asian population, if OSMS is an MS phenotype, an NMO spectrum disorder by 2015 classification, or a complement activating antibody to myelin oligodendrocyte glycoprotein (MOG-IgG) antibody-related disease. METHODS: We selected cases retrospectively with NMO and OSMS in the medical registry of patients with idiopathic inflammatory demyelinating diseases under follow-up since 1997 in Federal Hospital da Lagoa, the principal reference center for MS treatment in Rio de Janeiro, Brazil. OSMS has selective involvement of the optic nerve and spinal cord with no cerebral or cerebellar symptoms associated with small spinal cord lesions and negativity for the aquaporin-4 antibody (AQP4-IgG). NMO full-filled the revised criteria (2006) associated with longitudinally extensive transverse myelitis (LETM). We recorded the following data: ethnicity/skin color, neurologic impairment "at nadir" and "at recovery" of the index events (optic neuritis and transverse myelitis), long term disability, mortality, health quality of life scores by the SF-36 questionnaire, CSF IgG oligoclonal bands and serological AQP4-IgG and MOG-IgG antibodies tested by Cell-based assay. The last brain MRIs were classified as either satisfying or not satisfying MAGNIMS radiologic criteria for MS or typical or not typical for NMOSD. The new classification of NMO spectrum disorders (2015) was applied. RESULTS: Forty-one OSMS and 122 NMO cases were analyzed. OSMS affected mainly young white women, causing unilateral optic neuritis and partial myelitis with excellent recovery. After a mean disease duration of 20 years, 90% of the patients had free ambulation, and 70% had a mild disability or no disability. Only 7.2% presented a secondary progressive course, and no deaths occurred. All cases had negativity to AQP4-IgG and MOG-IgG biomarkers. 95% had resonance criteria for MS. OSMS differed from NMO by ethnicity, morbidity, and mortality: most were African descendants, with severe motor and visual dysfunction, and one third died. Only NMO cases full-filled the new NMOSD classification (52 AQP4-IgG positive, 29 AQP4-IgG negative, and 41 AQP4-IgG unknown). CONCLUSION: In Brazilian patients, OSMS and NMO are different immune-mediated diseases. OSMS is a milder MS phenotype.
Assuntos
Aquaporina 4/imunologia , População Negra/etnologia , Esclerose Múltipla/etnologia , Glicoproteína Mielina-Oligodendrócito/imunologia , Neuromielite Óptica/etnologia , Sistema de Registros , População Branca/etnologia , Adolescente , Adulto , Idoso , Povo Asiático/etnologia , Autoanticorpos/sangue , Brasil/etnologia , Criança , Pré-Escolar , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Esclerose Múltipla/fisiopatologia , Neuromielite Óptica/imunologia , Neuromielite Óptica/patologia , Neuromielite Óptica/fisiopatologia , Fenótipo , Índice de Gravidade de Doença , Adulto JovemRESUMO
The relationship between Sjögren’s syndrome (SS) and neuromyelitis optica spectrum disorder (NMOSD) is not completely understood. We report two patients with both conditions and review 47 other previously reported cases meeting currently accepted diagnostic criteria, from 17 articles extracted from PubMed. Out of 44 patients whose gender was informed, 42 were females. Mean age at onset of neurological manifestation was 36.2 years (10-74). Serum anti-AQP4-IgG was positive in 32 patients, borderline in 1, and negative in 4. Our Case 1 was seronegative for AQP4-IgG and had no non-organ-specific autoantibodies other than anti-SSB antibodies. Our Case 2 had serum anti-AQP4, anti-SSA/SSB, anti-thyreoglobulin and anti-acethylcholine-receptor antibodies, as well as clinical hypothyreoidism, but no evidence of myasthenia gravis. Our Cases and others, as previously reported in literature, with similar heterogeneous autoimmune response to aquaporin-4, suggest that SS and NMO co-exist in a common autoimmune milieu which is not dependent on aquaporin-4 autoimmunity.
A relação entre síndrome de Sjögren (SS) e espectro da neuromielite óptica (ENMO) ainda não é bem compreendida. Relatamos dois pacientes com ambas as condições e revisamos 47 casos que preenchem critérios diagnósticos das duas doenças, descritos em 17 artigos extraídos da PubMed. Dos 44 pacientes cujo gênero foi informado 42 eram mulheres. A idade média ao início das manifestações neurológicas foi 36,2 anos (10-74). O anticorpo anti-AQP4 foi positivo em 32 dos 37 pacientes, em 1 foi “borderline”. Nosso Caso 1 era soronegativo para AQP4-IgG, não tinha autoanticorpos não-órgão específicos, exceto anti-SSB. O Caso 2 era soropositivo para anticorpos anti-AQP4, anti-SSA/SSB, anti-tireoglobulina, e anti-receptor da acetilcolina; apresentava hipotireoidismo, mas não havia evidêncas de miastenia gravis. Nossos casos e outros similares, previamente relatados na literatura, com resposta autoimune heterogênea à aquaporina-4 sugerem que a SS e o ENMO coexistem em meio de autoimunidade não dependente da aquaporina-4.