Espectro de neuromielitis óptica: ¿seropositivo para la anticuaporina es una entidad diferente de los pacientes que son seronegativos? Una perspectiva de Colombia / Neuromyelitis optica spectrum disorder: Do patients positive and negative for anti–aquaporin-4 antibodies present distinct entities? A Colombian perspective

Introducción: La neuromielitis óptica es una enfermedad inflamatoria del sistema nervioso central, caracterizada por ataques de neuritis óptica y mielitis transversa longitudinalmente extensa. El descubrimiento del biomarcador diagnóstico anticuerpo anti-acuaporina-4 y los hallazgos imagenológicos en resonancia magnética cerebral han permitido el reconocimiento de un fenotipo clínico más amplio y detallado denominado espectro neuromielitis óptica. Objetivo: Determinar las características demográficas y clínicas de los pacientes diagnosticados con NMO/NMOSD, de acuerdo con la seropositividad del anticuerpo, en dos instituciones de cuarto nivel de complejidad en Bogotá. Métodos: Se realizó un estudio tipo serie de casos. Fueron incluidos aquellos pacientes > 18 años con diagnóstico de NMO/NMOSD, valorados en el Servicio de Neurología de dos hospitales de alta complejidad entre los años 2013 y 2017, con disponibilidad de estudios imagenológicos y resultados de serología. Se evaluaron variables demográficas, clínicas e imagenológicas, y se realizó un análisis de estas variables, según seropositividad del Ac-AQP4. Resultados: Se incluyeron 35 pacientes con NMO/NMOSD, la mediana de edad de inicio fue de 46,5 años (P25-P75 = 34,2-54,0), la mayoría de los pacientes tuvo manifestaciones clínicas a nivel sensitivo (n = 25) y motor (n = 26), en seis (n = 6) pacientes se identificó una enfermedad autoinmune concomitante. Se encontró seropositividad en 20 pacientes. Encontramos algunas diferencias en las características clínicas e imagenológicas, pero solo la edad y el compromiso de nervio óptico mostraron diferencia estadísticamente significativa (p = 0,03). Conclusiones: No se encontraron grandes diferencias clínicas, imagenológicas y de laboratorio, según la seropositividad del Ac-AQP4, excepto en la edad de inicio y el compromiso de nervio óptico (uni o bilateral), pero deben ser estudiadas de manera más detallada en poblaciones más amplias.(AU)

Introduction: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterised by attacks of optic neuritis and longitudinally extensive transverse myelitis. The discovery of anti–aquaporin-4 (anti-AQP4) antibodies and specific brain MRI findings as diagnostic biomarkers have enabled the recognition of a broader and more detailed clinical phenotype, known as neuromyelitis optica spectrum disorder (NMOSD). Objective: This study aimed to determine the demographic and clinical characteristics of patients with NMO/NMOSD with and without seropositivity for anti-AQP4 antibodies, in 2 quaternary-level hospitals in Bogotá. Methods: Our study included patients > 18 years of age and diagnosed with NMO/NMOSD and for whom imaging and serology results were available, assessed between 2013 and 2017 at the neurology departments of hospitals providing highly complex care. Demographic, clinical, and imaging data were gathered and compared in patients with and without seropositivity for anti-AQP4 antibodies. Results: The sample included 35 patients with NMO/NMOSD; the median age of onset was 46.5 years (P25-P75, 34.2-54.0); most patients had sensory (n = 25) and motor manifestations (n = 26), and a concomitant autoimmune disease was identified in 6. Twenty patients were seropositive for anti-AQP4 antibodies. Only age and presence of optic nerve involvement showed statistically significant differences between groups (p = .03). Conclusions: Clinical, imaging, and laboratory variables showed no major differences between patients with and without anti-AQP4 antibodies, with the exception of age of onset and presence of optic nerve involvement (uni- or bilateral); these factors should be studied in greater detail in larger populations.(AU)

Evolución clínica en neuromielitis óptica comparando el manejo con azatioprina o rituximab / Clinical evolution in neuromyelitis optica when comparing management with azathioprine and rituximab

RESUMEN INTRODUCCIÓN: El espectro de trastornos de neuromielitis óptica (NMOSD) es un grupo de enfermedades desmielinizantes, inflamatorias y autoinmunes, caracterizadas por episodios recurrentes de neuritis óptica y mielitis transversa longitudinal extensa, entre otras manifestaciones clínicas. Su tratamiento crónico se basa en el uso de terapias inmunosupresoras como azatioprina (AZA), micofenolato mofetilo (MFM) o rituximab (RTX). El objetivo del presente estudio es realizar un análisis comparativo de la respuesta al tratamiento con AZA o RTX. MATERIALES Y MÉTODOS: Se realizó un estudio observacional, analítico, retrospectivo, en el cual se incluyeron inicialmente 69 pacientes con diagnóstico confirmado de NMOSD. Tras aplicar los criterios de inclusión y exclusión 59 pacientes fueron incluidos en el análisis final. RESULTADOS: En el grupo de RTX se evidenció una mejoría importante en el estado funcional en comparación con el grupo de AZA, en el que se vio un empeoramiento de este al año de seguimiento. El perfil de seguridad fue similar entre ambos grupos, con una adherencia significativamente superior en el grupo de RTX. DISCUSIÓN: Los hallazgos del presente estudio respecto a las ventajas del uso de RTX sobre AZA se encuentran en concordancia con resultados de estudios previos reportados en la literatura. CONCLUSIONES: Los resultados respaldan el uso de RTX sobre AZA como terapia de mantenimiento para pacientes con NMOSD, al estar asociado principalmente con una mejoría notable en la funcionalidad de los pacientes, al igual que una mayor adherencia al tratamiento.

ABSTRACT INTRODUCTION: Neuromyelitis Optica Spectrum Disorders (NMOSD) is a group of inflammatory, autoimmune, and demyelinating disorders. Its hallmark behavior is characterized by recurrent episodes of optic neuritis and longitudinally extensive transverse myelitis, among other clinical manifestations. Chronic therapy is based primarily in immunosuppressive therapies such as azathioprine (AZA), mycophenolate mofetil (MMF), or rituximab (RTX). The goal of this study is to perform a comparative analysis of response rates to chronic treatment with either AZA or RTX. MATERIALS AND METHODS: A retrospective observational analytic study was designed with an initial cohort of 69 patients with a diagnosis of NMOSD. After application of the inclusion and exclusion criteria a total of 59 patients were finally included in the analysis. RESULTS: The RTX group had an improved functional status when compared to the AZA group; in the latter this feature worsened after a one-year follow-up. There was also a comparable safety profile between the two groups with a significantly greater adherence to RTX regimes. DISCUSSION: The findings of the current study as to the benefits of RTX in comparison to AZA are similar to the results of previous studies. CONCLUSION: These results favor the use of RTX as maintenance treatment of NMOSD, because of its greater benefit mainly in the improvement in functional status of patients, as well as a greater adherence to treatment.

Neuromyelitis optica spectrum disorder: do patients positive and negative for anti-aquaporin-4 antibodies present distinct entities? A Colombian perspective.

INTRODUCTION: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterised by attacks of optic neuritis and longitudinally extensive transverse myelitis. The discovery of anti-aquaporin-4 (anti-AQP4) antibodies and specific brain MRI findings as diagnostic biomarkers have enabled the recognition of a broader and more detailed clinical phenotype, known as neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: This study aimed to determine the demographic and clinical characteristics of patients with NMO/NMOSD with and without seropositivity for anti-AQP4 antibodies, in 2 quaternary-level hospitals in Bogotá. METHODS: Our study included patients > 18 years of age and diagnosed with NMO/NMOSD and for whom imaging and serology results were available, assessed between 2013 and 2017 at the neurology departments of hospitals providing highly complex care. Demographic, clinical, and imaging data were gathered and compared in patients with and without seropositivity for anti-AQP4 antibodies. RESULTS: The sample included 35 patients with NMO/NMOSD; the median age of onset was 46.5 years (P25-P75, 34.2-54.0); most patients had sensory (n = 25) and motor manifestations (n = 26), and a concomitant autoimmune disease was identified in 6. Twenty patients were seropositive for anti-AQP4 antibodies. Only age and presence of optic nerve involvement showed statistically significant differences between groups (P = .03). CONCLUSIONS: Clinical, imaging, and laboratory variables showed no major differences between patients with and without anti-AQP4 antibodies, with the exception of age of onset and presence of optic nerve involvement (uni- or bilateral); these factors should be studied in greater detail in larger populations.

Neuromielitis óptica y lupus eritematoso sistémico: caso clínico

La neuromielitis óptica (NMO) es una enfermedad desmielinizante del sistema Nervioso Central, con morbilidad, mortalidad alta, con respuesta favorable al tratamiento inmunosupresor y asociación infrecuente a enfermedades inmunológicas como Lupus Eritematoso Sistémico. Se reporta caso de un adolescente con diagnóstico de Neuromielitis óptica que presento durante su evolución Lupus Eritematoso Sistémico. Su evolución fue adecuada por la respuesta favorable a terapia inmunosupresora.

Optic neuromyelitis (NMO) is a demyelinating disease of the Central Nervous System, with morbidity, high mortality, favorable response to immunosuppressive treatment and infrequent association to immunological diseases such as Systemic Lupus Erythematosus. We report the case of a teenager with a diagnosis of Optic Neuromyelitis who presented Systemic Lupus Erythematosus during his evolution. Its evolution was adequate due to the favorable response to immunosuppressive therapy.

Optic neuromyelitis in relation with juvenile idiopathic arthritis: A case report

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.

Risk factors associated with permanent disability in neuromyelitis optica spectrum disorders.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease of the central nervous system. In NMOSD, a relapse results in increased disability. OBJECTIVE: To assess risk factors associated with permanent disability (PD) in patients with neuromyelitis optica spectrum disorders (NMOSD). METHODS: We evaluated 34 cases (who developed permanent disability) and 33 controls. The assessment included the following variables: sociodemographic data and characteristics of the disease. Logistic regression analysis was performed to adjust variables associated with PD. RESULTS: fifty-one percent developed PD during follow-up; 15 (22%) developed permanent visual disability, 13 (19%) developed permanent motor disability and 6 (9%) were restricted to wheelchair. Factors associated with PD in the crude analysis were: age at onset ≥ 50 years (OR 3.95, 95% IC 1.12-13.94, p= 0.032), time from onset to diagnosis ≥ 12 months (OR 3.30, 95% IC 1.13-9.64, p= 0.029), time from onset to treatment ≥ 60 months (OR 4.16, 95% IC 1.03-16.85, p= 0.045), EDSS ≥ 4.0 at the first appointment (OR 3.21, 95% IC 1.18-8.76, p= 0.022) and severe relapses during disease evolution (OR 5.72, 95% IC 1.98-16.57, p= 0.001). Factors associated with PD in the adjusted analysis were: age at onset ≥ 50 years (OR 5.82, 95% IC 1.30-26.05, p= 0.021), time from onset to diagnosis ≥ 12 months (OR 5.43, 95% IC 1.47-20.08, p= 0.011) and severe relapses during disease evolution (OR 6.65, 95% IC 1.98-22.31, p= 0.002). CONCLUSION: Half of patients with NMOSD may develop PD during disease evolution. Age of onset ≥ 50 years, delay to diagnosis ≥12 months and initial EDSS ≥ 4.0 constitute the strongest risk factors for PD.

Role of the gut microbiota in the development of various neurological diseases.

INTRODUCTION: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined. DEVELOPMENT: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis. CONCLUSIONS: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation.

The prevalence, incidence, and clinical assessment of neuromyelitis optica spectrum disorder in patients with demyelinating diseases.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is characterised by recurrent attacks of optic neuritis and transverse myelitis. The purpose of this work was to identify the incidence and prevalence of NMOSD and its clinical characteristics in the population treated for demyelinating diseases in Western Mexico. MATERIAL AND METHOD: A descriptive, retrospective study was carried out in the Department of Neurology, at the Sub-specialty Medical Unit, Specialties Hospital (known by its Spanish abbreviation UMAE-HE), of the National Western Medical Center (CMNO), Mexican Institute of Social Security (IMSS). A review of the electronic files for all patients with a diagnosis of NMOSD in 2019, was carried out in the State of Jalisco, Mexico. RESULTS: Fifty-eight patients with NMOSD were included in the study. The incidence was 0.71/100 000 (CI 0.60-0.85) and the prevalence was 1.09/100 000 (CI 0.84-1.42). There were 79.3% women, and 20.6% were men (P = .01). All (100%) patients presented with anti-aquaporin-4 immunoglobulin G, and 89.6% showed seropositivity for anti-aquaporin-4 (CI 82.6-94.9). Magnetic resonance imaging was performed on 100% of patients, where 34.4% were normal, and 65.5% (38) abnormal, presenting with non-specific subcortical lesions (P = 0.04). The initial clinical presentation was optic neuritis (ON) in 58.6%; where 31.0% was bilateral ON, 20.7% was left ON, and 6.9% were right ON; transverse myelitis in 26.0%, area postrema syndrome (APS) in 10.3%, among others. CONCLUSIONS: The incidence of NMOSD exceeds 0.71/100 000, the prevalence is low at 1.09/100 000, and NMOSD is predominantly found in women.

Papel de la microbiota intestinal en el desarrollo de diferentes enfermedades neurológicas / Role of the gut microbiota in the development of various neurological diseases

Introducción: En los últimos años la producción científica acerca de la microbiota y su relación con diversas enfermedades se ha disparado, hecho que se ha observado también entre las enfermedades neurológicas. Fruto de estas investigaciones ha surgido el concepto del eje intestino-cerebro, así como la existencia de una relación entre la microbiota intestinal y diversas enfermedades neurológicas, muchasde ellas sin etiopatogenia claramente definida. Desarrollo: Se revisa la implicación de la microbiota intestinal en el eje intestino-cerebro, así como en aquellas enfermedades neurológicas en que se ha descrito una alteración en la microbiota intestinal en estudios llevados a cabo en humanos; concretamente enfermedad de Parkinson, enfermedad de Alzheimer, esclerosis lateral amiotrófica, neuromielitis óptica y esclerosis múltiple. Conclusiones: En la actualidad el cuerpo de evidencia que relaciona la microbiota intestinal y diversas enfermedades neurológicas está creciendo notablemente. Existen interesantes estudios que relacionan la microbiota intestinal con la enfermedad de Parkinson, el Alzheimer, la neuromielitis óptica y la esclerosis múltiple, así como estudios controvertidos acerca del papel de las bacterias intestinales en la esclerosis lateral amiotrófica. En muchas de estas relaciones tiene un importante peso el papel de la modulación de la inflamación, especialmente de aquellas bacterias capaces de producir ácidos grasos de cadena corta. Aún quedan muchos interrogantes por dilucidar, como realizar estudios diseñados para demostrar causalidad, determinar el papel de hongos o virus y los posibles tratamientos con dieta, probióticos o trasplante de heces. (AU)

Introduction: In recent years, the scientific evidence supporting a relationship between the microbiota and various diseases has increased significantly; this trend has also been observed for neurological diseases. This has given rise to the concept of the gut-brain axis and the idea of a relationship between the gut microbiota and several neurological diseases whose aetiopathogenesis is yet to be clearly defined. Development: We review the role of the gut microbiota in the gut-brain axis and analyse those neurological diseases in which alterations in the gut microbiota have been described as a result of human studies: specifically, Parkinson's disease, Alzheimer disease, amyotrophic lateral sclerosis, neuromyelitis optica, and multiple sclerosis. Conclusions: The body of evidence linking the gut microbiota to various neurological diseases has grown considerably. Several interesting studies show a relationship between the gut microbiota and Parkinson's disease, Alzheimer disease, neuromyelitis optica, and multiple sclerosis, whereas other controversial studies implicate it in amyotrophic lateral sclerosis. Many of these studies place considerable emphasis on modulation of inflammation, particularly by bacteria capable of producing short-chain fatty acids. Despite these encouraging results, many questions remain, and there is a need to demonstrate causality, determine the role of fungi or viruses, and research possible treatment through diet, probiotics, or faecal microbiota transplantation. (AU)

Predictores de discapacidad en una cohorte con espectro de neuromielitis óptica / Predictors of disability in a cohort with neuromyelitis optica spectrum

Introducción: La discapacidad en el espectro de neuromielitis óptica (NMOSD) es frecuente y puede ser grave. Objetivo: Determinar factores asociados a mayor discapacidad en el NMOSD. Pacientes y métodosEstudio observacional, analítico, ambispectivo, en una cohorte de pacientes con NMOSD entre enero de 2015 y julio de 2021, utilizando una fuente secundaria para la revisión de variables y la escala extendida de discapacidad (EDSS) después del inicio y una fuente primaria, con una encuesta telefónica para la EDSS final y los datos faltantes. Se definió la discapacidad mayor cuando la puntuación de la EDSS era = 6. El análisis se realizó por medio de regresión logística con SPSS 25®. Resultados: Se analizó a 125 pacientes. La edad promedio de inicio fue 41 (desviación estándar: 14) años, con una relación mujer:hombre de 8:1. El 87% (109) era positivo para anticuerpos antiacuaporinas. La neuritis óptica (44,8%) y la mielitis transversa (39,2%) fueron las manifestaciones clínicas más frecuentes en el inicio. El 71,2% de los pacientes recibió tratamiento agudo en la primera recaída. La mediana de inicio del tratamiento crónico fue de 12 meses (rango intercuartílico: 3-60) y el 44% tuvo dificultades en el cumplimiento de la inmunosupresión. El 80,8% presentó recaídas y el 44% tenía una puntuación en la EDSS final = 6. La mediana de EDSS basal-final fue de 1 (rango intercuartílico, 0-3), con frecuencia hacia la acumulación de discapacidad. Se encontró asociación entre el curso con recaídas (odds ratio = 3,73; p = 0,011) y la EDSS basal alta (odds ratio = 1,54; p = 0,001) con una mayor discapacidad. En el análisis multivariado, una mayor EDSS basal y un curso con recaídas presentaron una probabilidad de discapacidad 1,6 y 5,3 veces mayor, respectivamente. Conclusiones: Las recaídas de la enfermedad y la EDSS alta después del primer episodio son predictores de discapacidad en el NMOSD.(AU)

Introduction: Disability in neuromyelitis optica spectrum disorder (NMOSD) is common and can be severe. Aim: To determine factors associated with increased disability in NMOSD. Patients and methods. Observational, analytical, ambispective study in a cohort of patients with NMOSD between January 2015 and July 2021, using a secondary source to review variables and the expanded disability status scale (EDSS) after onset and a primary source, with a telephone survey for the final EDSS and missing data. Major disability was defined as occurring when the EDSS score was ≥ 6. The analysis was performed by means of logistic regression with SPSS 25®. Results: A total of 125 patients were analysed. The average age at onset was 41 (standard deviation: 14) years, with a female-to-male ratio of 8:1. Of the total sample, 87% (109) were positive for anti-aquaporin antibodies. Optic neuritis (44.8%) and transverse myelitis (39.2%) were the most frequent clinical manifestations at onset. Altogether 71.2% of patients received acute treatment at their first relapse. Mean chronic treatment initiation was 12 months (interquartile range: 3-60) and 44% had difficulties with immunosuppression compliance. Of the total number of patients, 80.8% had relapses and 44% had a final EDSS score = 6. The median baseline-to-final EDSS score was 1 (interquartile range: 0-3), often towards disability accumulation. An association was found between a relapsing course (odds ratio = 3.73; p = 0.011) and a high baseline EDSS (odds ratio = 1.54; p = 0.0001) with increased disability. In the multivariate analysis, with a higher baseline EDSS and a relapsing course disability was 1.6 and 5.3 times more likely to occur, respectively. Conclusions: Disease relapses and high EDSS after the first episode are predictors of disability in NMOSD.(AU)

Experience with tocilizumab in patients with neuromyelitis optica spectrum disorders.

INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) are immune-mediated inflammatory disorders of the central nervous system involving astrocytes, B lymphocytes, anti-aquaporin 4, and such inflammatory mediators as interleukin-6. Several immunosuppressants are used in their treatment. Tocilizumab, an interleukin-6 receptor antagonist, may be a treatment option. METHOD: We performed an observational, retrospective study analysing parameters of effectiveness (annualised relapse rate, disability, and radiological progression) and safety of tocilizumab in patients with NMOSD in whom previous immunosuppressant treatment had failed. We aimed to evaluate the effectiveness and safety of tocilizumab in clinical practice in patients with NMOSD not responding to other immunosuppressants. RESULTS: Five patients with NMOSD were analysed. Sixty percent of patients were women; mean age at diagnosis was 50±5.3 years and mean progression time was 4.5±3.6 years. Previously administered immunosuppressants were rituximab (in all 5), cyclophosphamide (2), and azathioprine (1). Mean time of exposure to tocilizumab was 2.3±1 years. Mean annualised relapse rate was 1.8±1.3 in the year prior to the introduction of tocilizumab and 0.2±0.4 the year after (P<.05), representing a reduction of 88.9%. CONCLUSIONS: In our experience, tocilizumab is safe and effective in patients with NMOSD showing no response to other immunosuppressants.

Seasonal variation in attacks of neuromyelitis optica spectrum disorders and multiple sclerosis: Evaluation of 794 attacks from a nationwide registry in Argentina.

BACKGROUND: Identification of triggers that potentially instigate attacks in neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS) has remained challenging. We aimed to analyze the seasonality of NMOSD and MS attacks in an Argentinean cohort seeking differences between the two disorders. METHODS: A retrospective study was conducted in a cohort of NMOSD and MS patients followed in specialized centers from Argentina and enrolled in RelevarEM, a nationwide, longitudinal, observational, non-mandatory registry of MS/NMOSD patients. Patients with complete relapse data (date, month and year) at onset and during follow-up were included. Attack counts were analyzed by month using a Poisson regression model with the median monthly attack count used as reference. RESULTS: A total of 551 patients (431 MS and 120 NMOSD), experiencing 236 NMOSD-related attacks and 558 MS-related attacks were enrolled. The mean age at disease onset in NMOSD was 39.5 ± 5.8 vs. 31.2 ± 9.6 years in MS (p < 0.01). Mean follow-up time was 6.1 ± 3.0 vs. 7.4 ± 2.4 years (p < 0.01), respectively. Most of the included patients were female in both groups (79% vs. 60%, p < 0.01). We found a peak of number of attacks in June (NMOSD: 28 attacks (11.8%) vs MS: 33 attacks (5.9%), incidence rate ratio 1.82, 95%CI 1.15-2.12, p = 0.03), but no differences were found across the months in both disorders when evaluated separately. Strikingly, we observed a significant difference in the incidence rate ratio of attacks during the winter season when comparing NMOSD vs. MS (NMOSD: 75 attacks (31.7%) vs MS: 96 attacks (17.2%), incidence rate ratio 1.82, 95%CI 1.21-2.01, p = 0.02) after applying Poisson regression model. Similar results were observed when comparing the seropositive NMOSD (n = 75) subgroup vs. MS. CONCLUSIONS: Lack of seasonal variation in MS and NMOSD attacks was observed when evaluated separately. Future epidemiological studies about the effect of different environmental factors on MS and NMOSD attacks should be evaluated prospectively in Latin America population.

Perfil clínico y epidemiológico de los pacientes con diagnóstico de neuromielitis óptica / Clinical and epidemiological profile of patients with neuromyelitis optica diagnosis

INTRODUCCIÓN. El trastorno del espectro de neuromielitis óptica, enfermedad inflamatoria, desmielinizante, afecta al sistema nervioso central, frecuente en poblaciones no caucásicas como la ecuatoriana. El retraso en su diagnóstico y tratamiento provoca discapacidad que se puede prevenir. OBJETIVO. Determinar el perfil clínico y epidemiológico de los pacientes con diagnóstico de trastorno del espectro de neuromielitis óptica. MATERIALES Y MÉTODOS. Estudio descriptivo transversal. Población de 45 Historias Clínicas y una muestra de 41 de pacientes con diagnóstico de trastorno del espectro de neuromielitis óptica atendidos en la Unidad de Neurología del Hospital de Especialida-des Carlos Andrade Marín, período enero 2005 a diciembre 2019. Se realizó análisis univarial. Se aplicó el programa estadístico International Business Machines Statistical Package for the Social Sciences, versión 25. RESULTADOS. El 76,0% (31; 41) fueron mujeres. Datos promedios: edad 48,9 años; diagnóstico definitivo demoró 4,12 años, desde el inicio de los síntomas; tiempo de diagnóstico fue 3,17 años; 3,7 brotes en total; el 87,8% (36; 41) con un fenotipo recurrente. La media de duración de la enfermedad fue de 6,8 años. En el 70,7% (29; 41), se identificaron anticuerpos anti-AQP4 en suero mediante inmunofluorescencia directa, el 51,2% requirieron para la marcha apoyo uni o bilateral. El 43,9% (18; 41) debutó con neuritis óptica; el 31,7% (13; 41) presentaron mielitis como primer síntoma y el 24,4% (10; 41) la combinación de neuritis óptica y mielitis fueron los síntomas iniciales. CONCLUSIÓN. Se determinó el perfil clínico y epi-demiológico de los pacientes con diagnóstico de trastorno del espectro de neuromielitis óptica. Existió demora en el diagnóstico definitivo de los pacientes desde el inicio de los síntomas, lo que se tradujo en un aumento de la discapacidad.

INTRODUCTION. Neuromyelitis optica spectrum disorder, an inflammatory, demyelinating disease, affects the central nervous system, common in non-Caucasian popu-lations such as Ecuadorians. The delay in its diagnosis and treatment causes disabi-lity that can be prevented. OBJECTIVE. To determine the clinical and epidemiological profile of patients diagnosed with neuromyelitis optica spectrum disorder. MATERIALS AND METHODS. Cross-sectional descriptive study. Population of 45 Medical Records and a sample of 41 patients with a diagnosis of neuromyelitis optica spectrum disor-der seen at the Neurology Unit of the Carlos Andrade Marín Specialties Hospital, period from January 2005 to December 2019. Univariate analysis was performed. The statistical program International Business Machines Statistical Package for the Social Sciences, version 25 was used. RESULTS. 76,0% (31; 41) were women. Average data: age 48,9 years; definitive diagnosis took 4,12 years from the onset of symptoms; time to diagnosis was 3,17 years; 3,7 outbreaks in total; 87,8% (36; 41) with a recurrent phenotype. The average disease duration was 6,8 years. In 70,7% (29; 41), anti-AQP4 antibodies were identified in serum by direct immunofluorescence, 51,2% required uni- or bilateral su-pport for walking. Optic neuritis started in 43,9% (18; 41); 31,7% (13; 41) had myelitis as the first symptom and 24,4% (10; 41) the combination of optic neuritis and myelitis were the initial symptoms. CONCLUSION. The clinical and epidemiological profile of patients diagnosed with neuromyelitis optica spectrum disorder was determined. There was delay in the conclusive diagnosis of patients from the beginning of symptoms, which resulted in increased disability.

Neuromyelitis optica spectrum disorder: Do patients positive and negative for anti-aquaporin-4 antibodies present distinct entities? A Colombian perspective. / Espectro de neuromielitis óptica: ¿seropositivo para la anticuaporina es una entidad diferente de los pacientes que son seronegativos? Una perspectiva de Colombia.

INTRODUCTION: Neuromyelitis optica (NMO) is an inflammatory disease of the central nervous system characterised by attacks of optic neuritis and longitudinally extensive transverse myelitis. The discovery of anti-aquaporin-4 (anti-AQP4) antibodies and specific brain MRI findings as diagnostic biomarkers have enabled the recognition of a broader and more detailed clinical phenotype, known as neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: This study aimed to determine the demographic and clinical characteristics of patients with NMO/NMOSD with and without seropositivity for anti-AQP4 antibodies, in 2 quaternary-level hospitals in Bogotá. METHODS: Our study included patients > 18 years of age and diagnosed with NMO/NMOSD and for whom imaging and serology results were available, assessed between 2013 and 2017 at the neurology departments of hospitals providing highly complex care. Demographic, clinical, and imaging data were gathered and compared in patients with and without seropositivity for anti-AQP4 antibodies. RESULTS: The sample included 35 patients with NMO/NMOSD; the median age of onset was 46.5 years (P25-P75, 34.2-54.0); most patients had sensory (n = 25) and motor manifestations (n = 26), and a concomitant autoimmune disease was identified in 6. Twenty patients were seropositive for anti-AQP4 antibodies. Only age and presence of optic nerve involvement showed statistically significant differences between groups (p = .03). CONCLUSIONS: Clinical, imaging, and laboratory variables showed no major differences between patients with and without anti-AQP4 antibodies, with the exception of age of onset and presence of optic nerve involvement (uni- or bilateral); these factors should be studied in greater detail in larger populations.

Mielopatía por causa dual: neurosífilis y deficiencia de ácido fólico: reporte de caso / Dual cause myelopathy: neurosyphilis and folic acid deficiency: case report

RESUMEN La mielitis transversa es una lesión de la médula espinal que causa déficit completo (sensitivo, motor y esfinteriano) desde el nivel en el cual se presenta. Existe una variante denominada longitudinalmente extensa, la cual en la imagen por resonancia magnética (RM) afecta a tres o más cuerpos vertebrales. Se presenta el caso de un paciente con un síndrome medular secundario a neurosífilis y deficiencia de ácido fólico con lesiones medulares extensas.

SUMMARY Transverse myelitis is the spinal cord injury that causes complete deficit (sensory and motor) from the level in which it is present, classically associated with the loss of sphincter control. There is a variant known as longitudinally extensive, which in magnetic resonance imaging (MRI) affects three or more vertebral segments. We present the case of a patient with a medullary syndrome secondary to neurosyphilis with folate deficiency and extensive spinal cord injuries.

Autoimmune and demyelinating optic neuritis. / Neuritis ópticas desmielinizantes y autoinmunes.

The knowledge on demyelinating and autoimmune optic neuropathies has experienced a revolution the last decade since the discovery of anti-aquaporin 4 antibody. Improvements in diagnostic techniques, and the finding of new targets, along with advances in neuro-immunology have led to the detection of antibodies related to demyelinating diseases. A review is presented on the classical and new concepts in optic neuritis. The debate on the classification of demyelinating and autoimmune optic neuritis is presented. Furthermore, the updated diagnostic criteria in multiple sclerosis and neuro-myelitis optics are described. Finally, the latest insights into Myelin Oligodendrocyte Glycoprotein (MOG) disorders and chronic-recurring optic neuropathies (CRION) are highlited.

Mielitis longitudinal extensa de presentación muy tardía: Una entidad del espectro de la neuromielitis óptica / Extensive longitudinal myelitis of very late presentation. An entity of the spectrum of optic neuromyelitis

Las enfermedades del espectro neuromielitis óptica son trastornos inflamatorios del sistema nervioso central caracterizados por una grave desmielinización y daño axonal inmunomediado que afecta principalmente a los nervios ópticos y médula espinal. Suelen presentars e en edades tempranas, aunque existen algunas comunicaciones en la literatura de pacientes con presentaciones tardías. Presentamos el caso de una mujer de 78 años que consultó por un cuadro de paraparesia grave, trastornos sensitivos y retención urinaria. Se realizó una resonancia magnética de columna cervicodorsal que evidenció una lesión medular longitudinal extensa. Se descartaron otras causas secundarias, basadas en la clínica y en resultados de laboratorio. El dosaje de anticuerpos anti-acuaporina 4 resultó positivo. Se indicó tratamiento con glucocorticoides a altas dosis y plasmaféresis, y mantenimiento con rituximab, obteniendo escasa respuesta clínica. En pacientes con lesiones medulares extensas se deben contemplar múltiples diagnósticos diferenciales según la presentación clínica, hallazgos mediante estudios por imágenes y epidemiología. Asimismo, debe incluir la búsqueda de anticuerpos anti-acuaporina 4 y contra la glicoproteína de la mielina del oligodendrocito, ya que el pronóstico funcional de estos pacientes suele ser desfavorable debido al gran componente destructivo de las lesiones. En consecuencia, el tratamiento temprano es fundamental a fin de limitar el daño agudo y prevenir futuras recaídas, lo cual es especialmente importante en presentaciones tardías de esta entidad debido a la escasa reserva funcional y baja capacidad de remielinización.

Optic neuromyelitis spectrum diseases are inflammatory disorders of the central nervous system characterized by severe demyelination and immunomediated axonal damage that mainly affects the optic nerves and spinal cord. They usually appear at an early age, although there are some reports in the literature of patients with late presentations. We present the case of a 78-year-old woman who consulted for severe paraparesis, sensory disorders, and urinary retention. An MRI of the cervicodorsal spine was performed, showing extensive longitudinal spinal injury. Secondary causes based on clinical observations and laboratory studies were ruled out. The dosage of anti-aquaporin 4 antibodies was positive. Acute treatment with high-dose glucocorticoids and plasmapheresis was indicated, and maintenance with rituximab, obtaining little clinical response. In patients with extensive spinal injuries, multiple differential diagnoses should be considered according to the clinical presentation, findings through imaging studies and epidemiology. Likewise, it should include the search for anti-aquaporin 4 antibodies and against the oligodendrocyte myelin glycoprotein, since the functional prognosis of these patients is usually unfavourable due to the large destructive component of the lesions. Consequently, early treatment is essential in order to limit acute damage and prevent future relapses, which is especially important in late presentations of this entity due to the low functional reserve and low remyelination capacity.

Bases Fisiopatológicas Del Espectro De Neuromielitis Óptica: ¿Qué Sabemos? / Pathophysiological Basis Of Neuromyelitis Optica Spectrum Disorders: What do we know?

Resumen El espectro de Neuromielitis óptica (NMOSD por su sigla en inglés) corresponde a un conjunto de manifestaciones clínicas derivadas de un proceso inflamatorio y desmielinizante del sistema nervioso central, que causa lesiones primariamente en la médula espinal y nervios ópticos, pero también en otras regiones como tronco encefálico, diencéfalo o áreas cerebrales específicas. La mayoría de los pacientes con NMOSD son seropositivos para autoanticuerpos contra AQP4, el principal canal de agua de los astrocitos, sin embargo, existe un porcentaje no despreciable de pacientes, cercano al 25%, quienes son seronegativos para estos anticuerpos y en quienes la presencia de anticuerpos dirigidos contra mielina (anti-MOG) podrían tener un rol patogénico, el cual a la fecha no ha sido bien dilucidado. La evidencia científica actual, ha permitido reconocer que AQP4-IgG es patogénico en NMOSD, probablemente por un mecanismo que involucra citotoxicidad celular dependiente de la activación del complemento, generando infiltración leucocitaria, liberación de citokinas y disrupción de la barrera hemato-encefálica, lo cual lleva a muerte de oligodendrocitos, pérdida de mielina y muerte neuronal. Este artículo presenta una revisión basada en la evidencia, la cual enfatiza los principales aspectos de la patogénesis de NMOSD.

Neuromyelitis Optica Spectrum Disorders (NMOSD) is a set of clinical manifestations derived from an inflammatory and demyelinating process of the central nervous system that causes lesions primarily in spinal cord and optic nerves but also in other regions such as brainstem, diencephalon or specific brain areas. Most patients with NMOSD are seropositive for autoantibodies against AQP4, the major water channel of astrocytes, however there is a non-negligible percentage of patients, close to 25%, who are seronegative for these antibodies and in whom the presence of antibodies directed against myelin (anti-MOG) could have a pathogenic role that to date has not been well elucidated. Current scientific evidence has allowed recognize that AQP4-IgG is pathogenic in NMOSD, probably by a mechanism involving complement dependent cellular cytotoxicity, causing leucocyte infiltration, cytokine release and blood-brain barrier disruption, which leads to oligodendrocyte death, myelin loss and neuron death. This article presents an evidence-based review, which emphasizes the main aspects in NMOSD pathogenesis.

Use of ganglion cell layer analysis for diagnosing anti-glycoprotein neuromyelitis optica of oligodendrocyte myelin. / Uso del análisis de la capa de células ganglionares para el diagnóstico en la neuromielitis óptica anti-glucoproteína de la mielina del oligodendrocito.

The case concerns a 26-year-old patient with bilateral recurrent optic neuritis episodes in the context of suspected neuromyelitis optica. In the first outbreak, she had greatly impaired visual acuity of the left eye, as well as seeing ganglion cell layer damage in both eyes in the optic coherence tomography, with evidence of a possible extensive lesion in the optic chiasma. Likewise, MRI with contrast showed a great involvement of the left optic nerve that compromises the chiasma increasing the suspicion of a neuromyelitis origin. Althogh the anti-myelin oligodendrocyte glycoprotein (MOG) and anti-AQP4 (aquaporin-4) antibodies were negative at first, bilateral involvement of the ganglion cells suggested an extensive lesion that is more characteristic of seropositive anti-MOG neuromyelitis.

Clinical, Paraclinical and Imaging Characterization of a Population of Colombian Patients with Neuromyelitis Optica Spectrum Disorder at the Hospital Universitario San Ignacio, Bogotá, Colombia / Caracterización clínica, paraclínica e imaginológica de una población de pacientes Colombianos con espectro de Neuromielitis óptica del Hospital Universitario San Ignacio

SUMMARY INTRODUCTION: Neuromyelitis Optica (NMO) is an inflammatory syndrome of the central nervous system, different from multiple sclerosis, that is associated with aquaporin-4 IgG antibodies (AQP4-IgG). The new nomenclature defines a unified term of Neuromyelitis Optica Spectrum Disorder (NMOSD), seropositive or seronegative according to the AQP4-IgG positivity. OBJECTIVES: Demographic, clinical, imaging and cerebrospinal fluid (CSF) cytochemistry characterization of patients diagnosed with NMOSD at the Hospital Universitario San Ignacio (HUSI), Bogotá, Colombia, during 2006-2017. METHODS: A descriptive observational longitudinal study of patients diagnosed with NMO according to the International consensus diagnostic criteria for neuromyelitis optica spectrum disorders 2015 evaluated in HUSI during 2006-2017. An analysis of quantitative variables was performed with mean, standard deviation, median and interquartile range (IQR), and of qualitative variables with absolute numbers and percentages. A Wilcoxon sign-rank sum test was performed for paired data to evaluate the correlation between visual acuity (VA) and EDSS disability scale at admission and discharge after treatment. RESULTS: Data was collected for 37 patients. The mean age was 42 years-old. The form of presentation was optic neuritis (ON) in 81.1% of the cases. In patients who presented as ON, it was typical in 21.6%, atypical in 43.2% and bilateral in 18.9% of them. An average of 4.6 plasmapheresis (PPH) were performed; at discharge 45.9% presented a visual acuity (VA) lower than 20/800. The mean Expanded Disability Status Scale (EDSS) on admission was 2.8 (SD 1,4) and 2.2 (SD: 1,4). at discharge. CONCLUSION: Colombian NMOSD patients have shown an increasingly frequent phenotype variability Including a higher proportion of patients with bilateral optic neuritis, smaller number of patients with oligoclonal bands pattern II and with typical lesions of multiple sclerosis (MS) in MRI with seropositive NMO and a greater number of cases debuting with partial segment partial myelitis.

RESUMEN INTRODUCCIÓN: La Neuromielitis óptica (NMO) es un síndrome inflamatorio del sistema nervioso central diferente a la esclerosis múltiple que se asocia con anticuerpos IgG acuaporina-4 (AQP4-IgG). La nueva nomenclatura define el termino unificado de trastornos del espectro de Neuromielitis óptica (NMOSD), seropositiva o negativa de acuerdo a la positividad de AQP4-IgG. OBJETIVOS: Caracterización demográfica, clínica, imaginológica y del citoquímico de líquido cefalorraquídeo (LCR) en los pacientes con diagnóstico de NMOSD en el Hospital Universitario San Ignacio (HUSI), Bogotá, Colombia del año 2006-2017. MÉTODOS: Estudio observacional descriptivo longitudinal, pacientes con diagnóstico de NMO según criterios de Wingerchuck 2015, valorados en el HUSI, del 2006-2017. Se realizó análisis de variables cuantitativas con promedio, desviación estándar, mediana y percentil 25-75, las variables cualitativas con frecuencia absoluta y porcentajes. Se realizó prueba de Wilcoxon Signrank sum test para datos pareados para evaluar la correlación entre agudeza visual (AV) y escala de discapacidad de EDSS (Escala Expandida del Estado de Discapacidad) de ingreso y egreso posterior al tratamiento. RESULTADOS: 37 pacientes participaron. La edad promedio fue de 42 años. La forma de presentación fue neuritis óptica (NO) en el 81,1% de los casos. En los pacientes que se presentaron como NO fue típica en el 21,6%, atípica en 43,2% y bilateral 18,9% de los casos. Se realizó un promedio de 4,6 plasmaféresis (PMF), al egreso el 45,9% presentaron una agudeza visual (AV) menor de 20/800. EDSS de ingreso promedio 2,8 y el de egreso posterior a tratamiento fue de 2,2. CONCLUSIÓN: Existe variabilidad fenotípica, cada vez mas frecuente, en los pacientes con NMOSD. Incluyendo una mayor frecuencia de neuritis óptica bilateral, menor numero de pacientes con bandas oligoclonales patrón II positivas y con lesiones típicas de EMN en RMN con NMO seropositiva y una mayor presentación de casos debutando con mielitis parcial de segmento corto