Case report: Granzyme-B expression by T- and B- cells during severe AQP4-positive Neuromyelitis Optica spectrum disorder with fatal venous thromboembolism outcome.

Background: The expression of serine protease granzyme-B (GzmB) by circulating CD8+ T lymphocytes has been recently suggested as a biomarker for poor immunotherapy response and severe disability in patients with Neuromyelitis Optica spectrum disorders (NMOSD). In parallel, venous thromboembolism (VTE) has been reported mainly in NMOSD patients exhibiting transverse myelitis. Case presentation: Here, we describe an Aquaporin-4 positive (AQP4-positive) NMOSD patient who showed short myelitis (SM) and experienced a fatal pulmonary thromboembolism/lower extremity deep vein thrombosis during anti-CD20 treatment. Flow cytometry analyses from the peripheral blood revealed an enhanced cytotoxic behavior through circulating CD8+GzmB+ T, CD4+GzmB+ T lymphocytes, and residual CD19+GzmB+ B cells. Conclusions: Fatal VTE may be a rare outcome, particularly in patients exhibiting SM, and may share poorly understood immunological mechanisms with AQP4-positive NMOSD severity.

Prevalence of neuromyelitis optica spectrum disorder in antioquia between 2016 and 2018.

BACKGROUND: There are few epidemiological studies published in the world evaluating the prevalence of Neuromyelitis Optica Spectrum Disorder (NMOSD). The true prevalence of the disease is not known and the studies carried out are based on the diagnostic criteria used prior to 2015. OBJECTIVE: To determine the prevalence of NMOSD in Antioquia, from January 2016 to December 2018. METHODS: The prevalence of NMOSD in Antioquia was determined using the Capture-Recapture Method. Eight centers in the Department of Antioquia for the care of patients with neurological diseases were included. The data was collected between 2016 and 2018. RESULTS: A total of 221 consultation histories, 169 patients with a diagnosis of NMOSD were identified. The prevalence was 4.03 cases/100,000 inhabitants (95% confidence interval (CI) 3.3-4.8) of whom (87.5%), were women and the predominant race was Mestizo (81.6%). The most frequent initial presentation was optic neuritis (ON) (50.9%). Most of the patients had motor or visual disability (86.4%) and the treatment most used was Rituximab (47.9%). CONCLUSION: The prevalence of NMOSD in Antioquia is one of the highest reported in the world, except for the French Antilles. More studies are required to know the prevalence of this disease in the Colombian population.

PLEX: the best first-line treatment in nmosd attacks experience at a single center in Colombia.

OBJECTIVE: Primary outcome was to evaluate complete improvement at six months after acute treatment in NMOSD relapses. METHODS: Retrospective observational cohort study of patients with diagnosis of NMOSD admitted for acute attacks. We performed an explanatory analysis using the univariate, bivariate and multivariate logistic regression approach. We compared survival curves using the Kaplan Meier analysis and estimated the median time for the main outcome. RESULTS: In the univariate analysis, basal EDSS score, AQP4-IgG positivity, PLEX as a first-line treatment (IVMP + PLEX), less systemic complications related to acute treatment and total attack history were independently associated with complete improvement at six months. After adjusting for confounding variables and using multivariate analysis by Cox Regression, positive AQ4-IgG (HR 0.04, 95% CI: 0.02-0.66) and IVMP + PLEX (HR 5.1, 95% CI: 3.9-66.4), were kept as independent factors associated to time to complete improvement. Time from admission to PLEX initiation and complete improvement at six months had a median of seven days (95% CI: 5.2-8.8). In secondary effects, there were no statistical differences between the groups. CONCLUSIONS: PLEX + IVMP is the treatment of choice for NMOSD relapses and should be initiated as early as possible.

Trastorno del espectro de la neuromielitis óptica / Neuromyelitis Optica Spectrum Disorder: case report / Distúrbio do spectro da neuromilite óptica

El síndrome de Devic, también conocido como trastorno del espectro de la neuromielitis óptica (NMOSD, por sus sigla en inglés), es considerado una enfermedad inflamatoria, desmielinizante y autoinmune del sistema nervioso central que afecta en su mayoría los nervios ópticos, el quiasma óptico y la médula espinal. Si bien en algunos casos se puede simular un cuadro clínico similar a esclerosis múltiple, hoy en día se conocen aspectos imagenológicos, inmunológicos y patológicos que permiten establecer las diferencias entre estas dos entidades. Se presenta el caso de una mujer adulta mayor con antecedente de síndrome de Sjögren en manejo ambulatorio con corticoide y azatioprina, quien ingresa por cuadro clínico de mes y medio de evolución consistente en disestesias de predominio en miembros inferiores, alteración de la marcha y compromiso visual. Ante el compromiso neurológico, se decide realizar imágenes diagnósticas y perfil inmunológico, con reportes de resonancia magnética nuclear cervical y torácica con contraste que evidencian mielitis multifocal por compromiso cervical y torácico a nivel de C4 en T7-T8 con hiperdensidad centromedular sin realce, además de autoanticuerpos séricos dirigidos contra el canal acuaporínico (AQP4) positivos, dando así el diagnóstico de NMOSD.Se inició manejo con pulsos de metilprednisolona concomitantemente con plasmaféresis completando cinco sesiones. Sin embargo, ante la persistencia del cuadro clínico se inició manejo con un agente biológico selectivo que bloquea la actividad de los linfocitos B tipo rituximab con resolución parcial de los síntomas. Se discute, además, la evolución clínica e imagenológica de este caso ejemplar, así como los avances más notables en el diagnóstico y manejo

Devic's Syndrome, known as Optic Neuromyelitis Spectrum Disorder (NMOSD), is considered an inflammatory, demyelinating and autoimmune disease of the central nervous system (CNS) that mainly affects the optic nerves, the optic chiasm and the spinal cord. Although the said syndrome can sometimes simulate multiple sclerosis (MS), nowadays there are imagining, immunological and pathological aspects that allow to establish the differences between these two entities. In the present paper, the case an older adult woman with a history of Sjögren's syndrome in ambulatory care with corticosteroid and azathioprine, who is admitted for a month and a half of evolution consisting of dysesthesias of predominance in the lower limbs, ambulation impairment and visual compromise is presented . In view of the neurological compromise, it was decided to perform diagnostic imaging and immunological profile. The imaging suggested a report of cervical and thoracic MRI with contrast with evidence of multifocal myelitis due to cervical and thoracic involvement at the level of C4 and T7-T8, with a report of serum autoantibodies directed against the positive aquaporic channel (AQP4). All of the above is consistent with the diagnosis of Devic Syndrome or NMOSD. Treatment was implemented through methylprednisolone pulses alternated with plasmapheresis. Five sessions of the said treatment were completed. Given the persistence of the clinical picture, treatment with rituximab was initiated resulting in partial improvement of the symptoms. The clinical and imaging evolution of this case is also discussed, as well as breakingthrough advan-ces in its diagnosis and management

O síndrome de Devic, convencido cómo Transtorno do espectro da neuromielite ótica ou NMOSD pelo Nome em ingles é considerado uma doença inflamatória, desmielinizante e autoimune do sistema nervioso central (SNC) que afeta principalmente os nervos óticos, o quiasma ótico e a mêdula espinhal; embora em alguns casos pode se apresentar como sendo un caso clínico de esclerosis múltipla, hoje existem aspectos imagemológicos, inmunológicos e patológicos para diferenciar entre as duas condições. Apresentam-se o caso de una mulher idosa com antecedente de Síndrome de Sjögren com tratamento ambulatorio de corticoides, ingresada por quadro clínico de un mês e meio de evoluçao más disestêsias nos miembros inferiores com alteraçao para caminhada e comprometimento visual. Perante essa alteraçao neurológica, decide-se realizar imagens diagnósticas e perfil inmunológico com reporte de RMN cervical e torácica com contaste evidencia de mielitis multifocal por compromiso cervical e torácico a nivel de C4 e T7- T8 com hiperdensidade centromedular sem realce, reporte de autoanticuerpos séricos dirigidos contra o canal acuaporínico positivos, o diagnóstico foi Síndrome de Devic ou NMOSD. Perante esse scenário inicoou-se tratamento com pulsos de metlprednisolona junto con plasmaférese, por cinco sessões. No entanto, perante persistência do quadro clínico, inicoouse tratamento com agente biológico selectivo que bloqueia a atividade dos linfositos B tipo rituximab com resoluçao parcial dos síntomas. Discute-se a evoluçao clínica deste caso exemplar, mesmo cómo os avanços mais notáveis no diagnóstico e tratamento.IntroducciónEl síndrome de Devic, ahora conocido como trastor-no del espectro de la neuromielitis óptica (NMOSD, por su sigla en inglés), es una enfermedad inflamato-ria, desmielinizante y autoinmune del sistema nervioso central (SNC) que en su mayoría y de forma simultá-nea afecta los nervios ópticos, el quiasma óptico y la médula espinal (1). En los hallazgos imagenológicos en resonancia magnética nuclear (RMN) cerebral se evi-dencian lesiones mielínicas trasversas extensas longi-tudinales en tres o más segmentos vertebrales (2).El NMOSD fue reportado por primera vez en el siglo XIX, hacia 1894, luego de un reporte de caso; en esa ocasión se nombró síndrome de Devic y se describió como una variante de esclerosis múltiple (EM) (3,4). Keywords: Devic syndrome. Optic neuromyelitis, multiple sclerosis, antiacuaporin 4 antibodies, methylprednisolone, corticoid, plasmapheresis, rituximab Palavras Chave: sindrome de Devic, neuromielite óptica, esclerosis múltipla, anticorpos antiacuaporina 4, metlprednisolona, corticoides, plasmaférese, rituximab.

Anti-MOG (Myelin Oligodendrocyte Glycoprotein)-Positive Severe Optic Neuritis with Optic Disc Ischaemia and Macular Star.

A 44-year-old man presented with severe right visual loss. The right fundus examination showed marked optic disc oedema associated with partial macular star. Serological blood tests for infectious agents were all negative. Serum aquaporin-4 antibody was negative but anti-MOG (myelin oligodendrocyte glycoprotein) was positive. Magnetic resonance revealed extensive lesion in right optic nerve. There was no visual improvement after intravenous therapy. Patient had no further attacks after follow-up. Optic disc oedema with macular star is found in several infectious and non-inflammatory disorders, but it has not been reported in optic neuritis (ON) associated with autoantibodies to myelin oligodendrocyte glycoprotein (anti-MOG).

Neuromielitis Óptica: patología, diagnóstico y tratamiento en el siglo XXI / Optic Neuromyelitis: pathology, diagnosis and therapy in the XXI century

La neuromielitis óptica (NMO) o enfermedad de Devic, pertenece al grupo de las enfermedades desmielinizantes del sistema nervioso central, afecta de manera significativa los nervios ópticos y la médula espinal. Desde el siglo XIX cuando Eugene Devic dio a conocer una serie de casos en los que existía asociación de lesiones en los nervios ópticos y la medula espinal, la relación de la neuromielitis óptica (NMO) y la Esclerosis Múltiple (EM) ha sido controversial, considerándose una variante de esta última; datos recientes muestran que puede ser distinguida de la Esclerosis Múltiple (EM). Los síntomas de la NMO son por lo general más agudos y severos y la presencia de un autoanticuerpo específico en sangre llamado NMO-IgG tipo acuoporina-4 (AQP4) desempeña un rol muy importante en la patogenia de esta enfermedad,asimismo se encuentran varias características entre ellas de tipo clínico, de laboratorio, neuroimágenes y en la anatomía patológica que diferencian la esclerosis múltiple (EM) de esta enfermedad. La proporción entre mujeres y hombres es mayor de 4 a 1.La presentación clínica y el curso de la enfermedad puede ser con recaídas en 80-90% y en un 10-20% curso monofásico. La manifestación distintiva de la entidad NMO es la ocurrencia ya sea consecutiva o simultánea de NO (unilateral o bilateral) y la presencia de mielitis longitudinal extensa (Mle). La terapia con corticosteroides intravenosos normalmente es el tratamiento inicial para los ataques agudos de neuritis óptica o mielitis. La plasmaféresis es la terapia de rescate cuando no hay respuesta a los esteroides durante los ataques de neuromielitis óptica. Los agentes inmunosupresores se usan para la prevención de las recaídas.

Optic Neuromyelitis (NMO) or Devic’s disease, is a demyelinating disease of central nervous system, affects the optic nerves and spinal cord. Since the nineteenth century when Eugene Devic unveiled a series of cases in which there was an association of lesions in the optic nerves and spinal cord with relation of NMO and Multiple Sclerosis (MS) has been controversial, in some cases described like a variant of the latter but recent data show that can be distinguished from multiple sclerosis (MS). Symptoms of NMO are usually more acute and severe and then we can find a presence of a specific autoantibody called NMO-IgG, it is a blood type acuoporina-4 (AQP4) and plays an important role in the pathogenesis of this disease. Also in the new millennium are various types of clinical, laboratory, neuroimaging and pathological anatomy then differentiates multiple sclerosis (MS) of this disease. In the epidemiology the ratio of women to men is greater than 4 to 1.The clinical presentation and course of the disease can be relapsing by 80-90% and 10-20% monophasic course. The distinctive manifestation is the occurrence NMO entity either consecutively or simultaneously not (unilateral or bilateral) and the presence of extensive longitudinal myelitis. Intravenous corticosteroid therapy is usually the initial therapy for acute attacks of optic neuritis or myelitis. Plasmapheresis therapy is used when the steroids therapy no work during acute attacks of NMO. Immunosuppressive agents used to prevent relapses.