Enfermedad asociada a anticuerpos contra la glicoproteína de mielina de oligodendrocitos / Myelin oligodendrocyte glycoprotein antibody disease

Introducción: La enfermedad asociada a anticuerpos contra la glicoproteína de mielina del oligodendrocito (MOGAD, por sus siglas en inglés) es una entidad clínica recientemente identificada. La frecuencia de presentación del MOGAD es desconocida, pero se considera baja con respecto a otras enfermedades inflamatorias desmielinizantes. Materiales y métodos: Revisión narrativa de la literatura. Resultados: Las manifestaciones clínicas de esta condición son heterogéneas e incluyen neuritis óptica, mielitis, desmielinización multifocal del sistema nervioso central y encefalitis cortical. Se han descrito algunos hallazgos radiológicos que aumentan la sospecha diagnóstica, como el realce perineural del nervio óptico, el signo de la H en el cordón espinal y la resolución de lesiones T2 con el tiempo. El diagnóstico se basa en la detección de inmunoglobulinas G específicas contra MOG, en el contexto clínico adecuado. El tratamiento consiste en manejo de los ataques agudos con dosis altas de corticoides y en algunos casos se deberá considerar la inmunosupresión crónica, considerar la inmunosupresión crónica en pacientes con recurrencia o con discapacidad severa residual tras el primer evento. Conclusiones: En esta revisión narrativa se resumen los aspectos clave con respecto a la fisiopatología, las manifestaciones, el diagnóstico y el tratamiento de la MOGAD.

Introduction: The disease associated with antibodies against the myelin oligodendrocyte glycoprotein (MOGAD) is a recently identified clinical entity, with unknown frequency, but is considered low compared to other demyelinating inflammatory diseases. Materials And Methods: Narrative review. Results: The clinical manifestations are heterogeneous, ranging from optic neuritis or myelitis to multi-focal CNS demyelination or cortical encephalitis. There have been described characteristic MRI features that increase the diagnostic suspicion, such as perineural optic nerve enhancement, spinal cord H-sign or T2-lesion resolution over time. The diagnosis is based on the detection of specific G- immunoglobulins against MOG, in the suggestive clinical context. Acute treatment is based on high dose steroids and maintenance treatment is generally reserved for relapsing cases or patients with severe residual disability after the first attack. Conclusions: In this narrative review, fundamental aspects of pathophysiology, clinical and radiological manifestations, diagnosis and treatment of MOGAD are discussed.

Clinical spectrum of myelin oligodendrocyte glycoprotein antibody-associated disease in Brazil: a single-center experience / Espectro clínico de doença associada com anticorpos contra a glicoproteína de oligodendrócito de mielina no Brasil: uma experiencia de centro único

Abstract Background Anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibody-associated disease (MOGAD) is an immune-mediated neurological disorder with a broad spectrum of clinical presentation that is often difficult to distinguish from other demyelinating diseases, such as multiple sclerosis and neuromyelitis optica spectrum disorder. Objective To describe the clinical and paraclinical characteristics of MOGAD in a Brazilian tertiary center. Methods We retrospectively reviewed the records of adult and pediatric patients who tested positive for anti-MOG antibodies and presented with clinical and radiological diseases compatible with MOGAD. Results Forty-one patients (10 children) were included: 56% female, 58% Caucasian, mean age at onset 31 years (range 6-64), with a mean disease duration of 59.6 months (range 1-264 months). The most frequent onset presentation was optic neuritis (68%), acute disseminated encephalomyelitis (ADEM, 12%), and myelitis (10%). A monophasic disease course was observed in 49%. EDSS median was 2.1 at the last visit. Most patients (83%) were under continuous immunosuppressive treatment. Azathioprine was the first-line treatment in 59%. In all ADEM cases, conus, and root involvement was radiologically observed on MRI. Conclusion Brazilian MOGAD patients presented with a similar spectrum of previously reported MOGAD phenotypes. Conus and spinal root involvement seems to be frequently present in MOGAD-ADEM and could serve as radiologic characteristics of this clinical entity.

Resumo Antecedentes A doença associada ao anticorpo da glicoproteína da mielina de oligodendrócitos (anti-MOG; MOGAD) é uma doença neurológica imunomediada com um amplo espectro de apresentações clínicas que muitas vezes é difícil de distinguir de outras doenças desmielinizantes, como a esclerose múltipla e o distúrbio do espectro da neuromielite óptica. Objetivo Descrever as características clínicas e paraclínicas da MOGAD em um centro terciário brasileiro. Métodos Revisamos retrospectivamente os prontuários dos pacientes adultos e pediátricos que testaram positivos para anticorpos anti-MOG e apresentaram um quadro clínico e radiológico compatível com MOGAD. Resultados Quarenta e um pacientes (10 crianças) foram incluídos: 56% do sexo feminino, 58% caucasianos, idade média de início da doença foi 31 anos (intervalo de 6-64), com duração média da doença de 59,6 meses (intervalo de 1-264 meses). A apresentação inicial mais frequente foi neurite óptica (68%), seguida pela encefalomielite disseminada aguda (ADEM, 12%) e mielite (10%). Um curso monofásico da doença foi observado em 49%. EDSS foi de 2,1 na última visita. A maioria dos pacientes (83%) estava sob tratamento imunossupressor contínuo. Azatioprina foi o tratamento de primeira linha em 59%. Em todos os casos de ADEM, o envolvimento do cone medular e das raízes espinhais foi observado radiologicamente na ressonância magnética. Conclusão Os pacientes brasileiros com MOGAD apresentam um espectro clínico e radiológico semelhante aos fenótipos de MOGAD relatados anteriormente. O envolvimento do cone e das raízes espinhais parece estar frequentemente presente no MOGAD-ADEM e poderia servir como característica radiológica nesta entidade.

AQP4-IgG NMOSD, MOGAD, and double-seronegative NMOSD: is it possible to depict the antibody subtype using magnetic resonance imaging? / NMOSD AQP4-IgG, MOGAD e NMOSD duplo soronegativo: é possível caracterizar o tipo de anticorpo pela ressonância magnética?

Abstract Background There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. Objective To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. Methods A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. Results In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). Conclusion The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.

Resumo Antecedentes Há sobreposição clínica e radiológica entre as doenças desmielinizantes. No entanto, seus mecanismos fisiopatológicos são diferentes e apresentam prognósticos e demandas de tratamento distintos. Objetivo Investigar as características de imagens de RM dos pacientes com doença associada à glicoproteína de oligodendrócito de mielina (MOGAD), a doenças do espectro da neuromielite óptica positivas para antiaquaporina-4 imunoglobulina G (AQP4-IgG NMOSD), e pacientes duplamente soronegativos. Métodos Estudo retrospectivo e transversal para analisar as características e frequência das lesões do sistema nervoso central (SNC). Dois neurorradiologistas avaliaram consensualmente as imagens do cérebro, das órbitas e da medula espinhal. Resultados Ao todo, foram incluídos 68 pacientes(25 com AQP4-IgG NMOSD, 28 com MOGAD e 15 duplo-soronegativos). Há diferenças na apresentação clínica entre os grupos. O grupo MOGAD demonstrou menor frequência de comprometimento do cérebro (39.2%) comparado com o AQP4-IgG NMOSD (p = 0.002), com predomínio da distribuição das lesões nas regiões subcortical/justacortical, mesencéfalo, pedúnculos cerebelares médios e cerebelo. O grupo duplo-soronegativo demonstrou maior frequência de comprometimento do cérebro (80%), com lesões de maiores dimensões e com morfologia tumefeita, além de neurite óptica com maior extensão (p = 0.006). O grupo AQP4-IgG NMOSD demonstrou neurite óptica com predomínio na região óptico-quiasmática e as lesões encefálicas acometeram predominantemente as regiões hipotalâmica e área postrema (MOGAD versus AQP4-IgG NMOSD p = 0.013). Além disso, foram observadas mais lesões na medula espinhal (78.3%) e a presença da "bright spotty lesion" foi um achado primordial para a sua diferenciação com os pacientes MOGAD (p = 0.003). Conclusão A análise pormenorizada das características das lesões por RM dos pacientes com doenças desmielinizantes imunomediadas fornece informações fundamentais que auxiliam os médicos no diagnóstico diferencial em um momento oportuno.

Myelin oligodendrocyte glycoprotein antibody-associated optic neuritis: an update / Neurite óptica associada com anticorpo contra a glicoproteína oligondendrócita da mielina: uma breve atualização

ABSTRACT Myelin oligodendrocyte glycoprotein-immunoglobulin G (IgG)-associated optic neuritis has been established as a new entity of immune-mediated optic neuropathy. Patients usually present with recurrent optic neuritis, often bilaterally with initially severe vision loss and optic disc edema. However, in contrast to aquaporin 4-IgG-seropositive neuromyelitis optica spectrum disorder, visual recovery tends to be more favorable, with good response to steroid treatment. Another important differential diagnosis of myelin oligodendrocyte glycoprotein-IgG--associated optic neuritis is multiple sclerosis. Close monitoring for signs of relapse and long-term immunosuppression may be considered to maintain optimal visual function. The diagnosis can be made on the basis of the presence of a specific, usually serological, antibody against myelin oligodendrocyte glycoprotein (IgG; cell-based assay), and a demyelinating event (optic neuritis, myelitis, brainstem syndrome, or cortical lesions with seizures). The clinical spectrum of this newly recognized inflammatory demyelinating disease is expanding rapidly. We briefly review the epidemiological characteristics, clinical manifestations, diagnostic considerations, and treatment options of myelin oligodendrocyte glycoprotein-IgG-associated optic neuritis.

RESUMO A neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG foi estabelecida como uma nova entidade de neuropatia óptica imunomediada. Tipicamente os pacientes apresentam neurite óptica recorrente, muitas vezes bilateral, com perda de visão frequentemente severa e alta prevalência de edema do disco óptico na fase aguda. No entanto, em contraste com neuromyelitis optica spectrum disorder associada com presença de anticorpo contra aquaporina 4, a recuperação visual tende a ser mais favorável e responde bem ao tratamento com corticoide em altas doses. A esclerose múltipla representa outro importante diagnóstico diferencial de glicoproteína de oligodendrócito de mielina-IgG. O diagnóstico pode ser feito com base na presença de um anticorpo específico, geralmente sorológico contra glicoproteína de oligodendrócito de mielina (IgG, ensaio baseado em células), e presença de evento desmielinizante (neurite óptica, mielite, síndrome do tronco cerebral, lesões corticais com convulsões). O espectro clínico desta doença desmielinizante inflamatória recém-reconhecida está se expandindo rapidamente. Faremos uma breve revisão das características epidemiológicas, manifestações clínicas, considerações diagnósticas e opções de tratamento da neurite óptica associada à glicoproteína de oligodendrócito de mielina-IgG.

Neuromyelitis optica spectrum disorders: a review with a focus on children and adolescents / Espectro da neuromielite óptica: uma revisão com ênfase em crianças e adolescentes

Abstract Neuromyelitis optica spectrum disorder (NMOSD) is a rare and severe inflammatory disorder of the central nervous system (CNS). It is strongly associated with anti-aquaporin 4 antibodies (AQP4-IgG), and it mainly affects young women from non-white ethnicities. However, ~ 5 to 10% of all cases have onset during childhood. Children and adolescents share the same clinical, radiologic, and laboratory presentation as adults. Thus, the same NMOSD diagnostic criteria are also applied to pediatric-onset patients, but data on NMOSD in this population is still scarce. In seronegative pediatric patients, there is a high frequency of the antibody against myelin oligodendrocyte glycoprotein (MOG-IgG) indicating another disease group, but the clinical distinction between these two diseases may be challenging. Three drugs (eculizumab, satralizumab, and inebilizumab) have been recently approved for the treatment of adult patients with AQP4-IgG-positive NMOSD. Only satralizumab has recruited adolescents in one of the two pivotal clinical trials. Additional clinical trials in pediatric NMOSD are urgently required to evaluate the safety and efficacy of these drugs in this population.

Resumo O espectro da neuromielite óptica (ENMO) é uma rara e grave doença inflamatória do sistema nervoso central (SNC), fortemente associada ao anticorpo anti-aquaporina 4 (AQP4-IgG) e que afeta preferencialmente mulheres jovens de etnias não-caucasianas. No entanto, aproximadamente de 5 a 10% de todos os casos se iniciam na infância. Crianças e adolescentes compartilham as mesmas características clínicas, radiológicas e laboratoriais dos adultos. Além disso, o mesmo critério diagnóstico de ENMO é aplicado para pacientes com início na infância. No entanto, dados da população pediátrica são escassos. Em pacientes pediátricos soronegativos, existe uma alta frequência de positividade ao anticorpo contra a glicoproteína na mielina do oligodendrócito (MOG-IgG), indicando outra patologia; porém, a distinção clínica entre as duas doenças é desafiadora. Três medicações (eculizumabe, inebilizumabe e satralizumabe) foram recentemente aprovadas para pacientes adultos com AQP4-IgG. Apenas um dos ensaios pivotais do satralizumabe recrutou adolescentes. Novos ensaios clínicos em pacientes pediátricos com ENMO são necessários para avaliar a segurança e eficácia destas drogas nesta população.

Differential diagnosis of demyelinating diseases: what's new? / Diagnóstico diferencial das doenças desmielinizantes: o que há de novo?

ABSTRACT Background: Acquired demyelinating disorders lead to overlapping visual, pyramidal, sensory, autonomic, and cerebellar deficits and may lead to severe disability. Early diagnosis and start of treatment are fundamental towards preventing further attacks and halting disability. Objective: In this paper we provide an updated overview of the differential diagnoses of acquired demyelinating disorders. Methods: We performed a critical targeted review of the diagnoses of the most prevalent demyelinating disorders: multiple sclerosis (MS), neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). Results: We discuss the workup, diagnostic criteria and new biomarkers currently being used for the diagnosis of these disease entities taking into account the particularities of the Brazilian population and healthcare system. Conclusion: A comprehensive analysis of medical history, physical examination, biomedical and imaging data should be performed to obtain differential diagnosis. Diagnostic criteria should be mindfully employed considering ethnic and environmental particularities of each patient.

RESUMO Antecedentes: Doenças desmielinizantes adquiridas levam a déficits visuais, piramidais, sensitivos, autonômicos e cerebelares que se sobrepõem e podem conduzir a grave incapacidade. O diagnóstico e o início de tratamento precoces são fundamentais para a prevenção de surtos e ocorrência de incapacidade. Objetivo: Neste artigo, apresentamos uma visão geral atualizada sobre o diagnóstico diferencial de doenças desmielinizantes adquiridas. Métodos: Realizamos uma revisão crítica sobre o diagnóstico das doenças desmielinizantes mais prevalentes: esclerose múltipla (EM), doença do espectro neuromielite óptica (NMOSD) e doença associada ao anticorpo contra a glicoproteína da mielina do oligodendrócito (MOGAD). Resultados: Discutimos a investigação, os critérios diagnósticos e os novos biomarcadores atualmente empregados para o diagnóstico dessas doenças, levando em conta as particularidades da população e sistema de saúde brasileiros. Conclusão: Uma análise minuciosa do histórico médico, exame neurológico e exames biomédicos e de imagem deve ser realizada para se fazer um diagnóstico diferencial de doença desmielinizante. Critérios diagnósticos devem ser empregados cautelosamente considerando-se particularidades étnicas e ambientais de cada paciente.

Rol de la neuroglia en el trastorno del espectro autista / Role of neuroglia in autism spectrum disorder

RESUMEN: El trastorno del espectro autista (TEA) se caracteriza por presentar déficits persistentes en la comunicación y en la interacción social. Además, patrones de comportamiento, intereses o actividades de tipo restrictivo o repetitivo. Su etiología es compleja y heterogenia, y los mecanismos neurobiológicos que dan lugar al fenotipo clínico aún no se conocen por completo. Las investigaciones apuntan a factores genéticos y ambientales que afectan el cerebro en desarrollo. Estos avances coinciden con un aumento en la comprensión de las funciones fisiológicas y el potencial patológico de la neuroglia en el sistema nervioso central (SNC) que llevó a la noción de la contribución fundamental de estas células en el TEA. Así, el objetivo de este artículo fue revisar brevemente los factores de riesgo clave asociados al TEA y luego, explorar la contribución de la neuroglia en este trastorno. Se destaca el rol de los astrocitos, los microglocitos y los oligodendrocitos en el control homeostático del SNC, en la regulación inmunitaria del cerebro y en la mielinización axonal, así como el mal funcionamiento y las alteraciones morfológicas de estas células en los cerebros autistas.

SUMMARY: Autism spectrum disorder (ASD) is characterized by persistent deficits in communication and social interaction, as well as restrictive or repetitive activities or interests. Its etiology is complex and heterogeneous, and the neurobiological mechanisms that give rise to the clinical phenotype are not yet fully understood. Research points to genetic and environmental factors that affect the developing brain. These advances are consistent with an enhanced understanding of the physiological functions and pathological potential of neuroglia in the central nervous system (CNS) which supports the conclusion of the contribution of these cells in ASD. Therefore, the objective of this article was to briefly review the key risk factors associated with ASD and then explore the contribution of glia in this disorder. The role of astrocytes, microgliocytes and oligodendrocytes in the homeostatic control of the CNS in the immune regulation of the brain and in axonal myelination, as well as malfunction and morphological alterations of these cells in autistic brains are emphasized.

Altered oligodendrocytes in spinal enlargements of streptozotocin diabetic rats / Oligodendrocitos alterados en la intumescencia espinal de ratas diabéticas con estreptozotocina

SUMMARY: Disturbances of sensory and motor nerve conduction velocity in the spinal cord as well as degenerated myelin sheaths are observed in diabetic patients and animal models. Indeed, oligodendrocytes (OLs), which are important neuroglial cells, generate myelin in the central nervous system. Spinal enlargement, including cervical and lumbar enlargements, innervates all limbs. Thus, the purposes of this study were to examine and compare the ultrastructural alterations of OLs in spinal enlargements of streptozotocin (STZ)- induced diabetic rats and controls. Thirteen male Sprague-Dawley rats were induced with STZ in citrate buffer and six control rats were injected with the same buffer solution. All rats were sacrificed after inductions at four (short-term DM) and twenty-four weeks (long-term DM). The selected spinal enlargements were processed for transmission electron microscopy. The OL alterations in both the cervical and lumbar enlargements were apparently the same. In short-term DM, the nuclei of OLs became swelled with chromatin clumping. Cytoplasmic organelles were moderately damaged. In long-term DM, OLs contained shrinkage nuclei with thick heterochromatin clumping. Severely degenerated mitochondria with disrupted cristae and broken membranes were observed. Moreover, distended and fragmented rough endoplasmic reticulum were observed, and large clear areas were present in the cytoplasm. Additionally, the loosening, splitting, and destruction of myelin lamellae were found. This study can provide important preliminary information about the alteration of OLs in the spinal cords of diabetic patients, which might be involve in the impairments of sensory and motor conduction velocities in these individuals.

RESUMEN: En pacientes diabéticos y modelos animales se observan alteraciones de la velocidad de conducción nerviosa sensorial y motora en la médula espinal, así como vainas de mielina degeneradas. De hecho, los oligodendrocitos (OL), que son importantes células neurogliales, generan mielina en el sistema nervioso central. La intumescencia espinal, a nivel cervical y lumbar, inerva los miembros. Por lo tanto, los propósitos de este estudio fueron examinar y comparar las alteraciones ultraestructurales de los OL en la intumescencia espinal de ratas diabéticas inducidas por estreptozotocina (STZ) y controles. Se indujeron trece ratas macho Sprague-Dawley con STZ en tampón citrato y se inyectaron seis ratas de control con la misma solución tampón. Todas las ratas se sacrificaron después de la inducción a las cuatro (DM a corto plazo) y a las veinticuatro semanas (DM a largo plazo). Las ampliaciones de la columna seleccionadas se procesaron para microscopía electrónica de transmisión. Las alteraciones de OL en las intumescencias cervical y lumbar eran aparentemente las mismas. En la DM a corto plazo, los núcleos de los OL se hincharon con la acumulación de cromatina. Los orgánulos citoplasmáticos sufrieron daños moderados. En la DM a largo plazo, los OL contenían núcleos de contracción con aglutinación de heterocromatina gruesa. Se observaron mitocondrias severamente degeneradas con crestas y membranas rotas. Además, se observó un retículo endoplásmico rugoso distendido y fragmentado, y estaban presentes grandes áreas claras en el citoplasma. Además, se encontraron el aflojamiento, la división y la destrucción de las laminillas de mielina. Este estudio puede proporcionar información preliminar importante sobre la alteración de los OL en la médula espinal de los pacientes diabéticos, que podría estar involucrada en las alteraciones de las velocidades de conducción sensorial y motora en estos individuos.

Neuritis óptica recurrente posterior a encefalomielitis diseminada aguda en pediatría. Reporte de un caso / Recurrent optic neuritis after acute disseminated encephalomyelitis in pediatrics. A case report

Abstract: Optic Neuritis (ON) is a condition caused by the inflammation of the optic nerve, causing diminished visual acuity and ocular pain. It is tightly related to Multiple Sclerosis (MS), often being the first demyelinating event. There is a 31% risk of recurrence during the first 10 years after the diagnosis, and 48% of the patients end up being diagnosed with Multiple Sclerosis1. Imaging studies like brain MRI (Magnetic Resonance Imaging) have a critical role in the diagnosis and prognosis of ON, as well as in the recognition of MS.2 The patient is a 11-year-old girl with recurrent ON and past medical history of Acute Disseminated Encephalomyelitis (ADEM) when she was 5 years old. ON diagnosis was based on clinical findings as well as on ophtalmologic, electrophysiologic and imaging studies. The recurrent episodes of ON improved after the use of high dose steroids. Recurrences were observed after titration of the dose, but remission was achieved after adjustment of treatment. During one of the recurrent episodes, blood work was performed to evaluate possible underlying infectious, demyelinating or autoinmmune process. Anti-MOG antibodies were found positive. The patient at the moment is not presenting with any other criteria suggesting MS or Optic Neuromyelitis, but long term follow up is adviced. Key words: Optic neuritis (ON), multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), magnetic resonance imaging (MRI), cerebrospinal fluid (CSF), right eye (RE); visual acuity (VA), optic neuromyelitis (ONM)

MOG-IgG associated optic neuritis is not multiple sclerosis / Neurite óptica associada ao MOG-IgG não é esclerose múltipla

ABSTRACT Autoantibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) have been reported in patients with inflammatory central nervous system disorders including isolated optic neuritis (ON). We compared our MOG-IgG ON patients with multiple sclerosis (MS) patients presenting with ON. Methods and results: Among the total of 38 patients with optic neuropathies, six patients with isolated ON were MOG-IgG positive and eight patients with ON fulfilled the diagnostic criteria for MS. All MS patients were negative for MOG-IgG using a cell-based assay. When compared with the MS group, the MOG-IgG patients were older (mean 47 years), more frequently male (ratio 2:1) and had a higher frequency of bilateral and/or recurrent ON. The brain magnetic resonance imaging of all MOG-IgG positive patients was normal or had only unspecific white matter T2 lesions. Conclusion: These findings suggest that MOG-IgG is a biomarker of an inflammatory demyelinating CNS disease distinct from MS.

RESUMO Autoanticorpos contra a glicoproteína da mielina do oligodendrócito (MOG-IgG) têm sido descritos em pacientes com neurite óptica (NO) isolada, entre outras doenças inflamatórias do sistema nervoso central. Comparamos os nossos pacientes com NO MOG-IgG positivos com pacientes com NO associada a esclerose múltipla (EM). Materias e métodos: De um total de 38 pacientes com neuropatia óptica, seis foram MOG-IgG positivos e oito preencheram critérios diagnósticos para EM. Todos os pacientes com EM foram negativos para MOG-IgG (ensaio baseado em células). Quando comparados ao grupo com EM, os pacientes MOG-IgG positivos apresentam idade mais avançada (mediana de 47 anos) e tiveram uma frequência maior de NO bilateral e/ou recorrente. Houve predomínio masculino (relação 2:1). A ressonância magnética de encéfalo de todos os pacientes MOG-IgG positivos foi normal ou demonstrou apenas lesões inespecíficas em T2. Conclusão: Nossos achados sugerem que o MOG-IgG é um biomarcador de doença desmielinizante diferente da EM.

Características de la estructura molecular de las proteínas E del virus del Zika y E1 del virus de la rubéola y posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso / E-ZIKV and E1-RV proteins molecular structure and their potential implications in neurotropism and nervous system disorders

Resumen Introducción. El virus del Zika (ZIKV) es un flavivirus con envoltura, transmitido a los seres humanos principalmente por el vector Aedes aegypti. La infección por ZIKV se ha asociado con un gran neurotropismo y con efectos neuropáticos, como el síndrome de Guillain-Barré en el adulto y la microcefalia fetal y posnatal, así como con un síndrome de infección congénita similar al producido por el virus de la rubéola (RV). Objetivo. Comparar las estructuras moleculares de la proteína de envoltura E del virus del Zika (E-ZIKV) y de la E1 del virus de la rubéola (E1-RV), y plantear posibles implicaciones en el neurotropismo y en las alteraciones del sistema nervioso asociadas con el ZIKV. Materiales y métodos. La secuencia de aminoácidos de la proteína E-ZIKV (PDB: 5iZ7) se alineó con la de la glucopreteína E1 del virus de la rubéola (PDB: 4ADG). Los elementos de la estructura secundaria se determinaron usando los programas Vector NTI Advance®, DSSP y POSA, así como herramientas de gestión de datos (AlignX®). Uno de los criterios principales de comparación y alineación fue la asignación de residuos estructuralmente equivalentes, con más de 70 % de identidad. Resultados. La organización estructural de la proteína E-ZIKV (PDB: 5iZ7) fue similar a la de E1-RV (PDB: 4ADG) (70 a 80 % de identidad), y se observó una correspondencia con la estructura definida para las glucoproteínas de fusión de membrana de clase II de los virus con envoltura. E-ZIKV y E1-RV exhibieron elementos estructurales de fusión muy conservados en la región distal del dominio II, asociados con la unión a los receptores celulares de entrada del virus de la rubéola (glucoproteína de mielina del oligodendrocito, Myelin Oligodendrocyte Glycoprotein, MOG), y con los receptores celulares Axl del ZIKV y de otros flavivirus. Conclusión. La comparación de las proteínas E-ZIKV y E1-RV es un paso necesario hacia la definición de otros factores moleculares determinantes del neurotropismo y la patogenia del ZIKV, el cual puede contribuir a generar estrategias de diagnóstico, prevención y tratamiento de las complicaciones neurológicas inducidas por el ZIKV.

Abstract Introduction: Zika virus (ZIKV) is an enveloped flavivirus transmitted to humans mainly by Aedes aegypti. ZIKV infection has been associated with high neurotropism and neuropathic effects such as the Guillain-Barré syndrome in adults, and fetal and postnatal microcephaly and the congenital Zika virus syndrome similar to that produced by rubella virus (VR). Objective: To compare Zika virus membrane protein E (E-ZIKV) and rubella virus membrane protein E1 (E1-RV), and to propose possible implications for neurotropism and nervous system disorders associated with ZIKV infections. Materials and methods: The amino acid sequence of E-ZIKV protein (PDB: 5iZ7) was aligned to that of rubella virus glycoprotein E1 (PDB: 4ADG). The secondary structure elements were determined using the programs Vector NTI Advance®, DSSP, and POSA, and integrated data management tools (AlignX®). One of the main comparison and alignment criteria was the allocation of structurally equivalent residues with more than 70% identity. Results: E-ZIKV structural organization (PDB: 5iZ7) was similar to that of E1-RV (PDB: 4ADG) (70%-80% identity), and it was consistent with relevant structural features of viral membrane class II fusion glycoproteins. E-ZIKV and E1-RV exhibited highly conserved fusion structural elements at the distal region of domain II, which has been associated with the RV myelin oligodendrocyte glycoprotein and Axl cell receptors in ZIKV and other flaviviruses. Conclusion: The comparison of E-ZIKV and E1-RV proteins constitutes an essential step towards the definition of ZIKV neurotropism and pathogenesis molecular determinants, and for the adoption of diagnosis, prevention and treatment strategies against neurological complications induced by ZIKV infection.

Os possíveis papéis da S100B na esquizofrenia / Potential roles of S100B in schizophrenia

Evidências científicas do aumento da concentração da proteína S100B no sangue de pacientes esquizofrênicos são muito consistentes. No passado essa informação era principalmente considerada como reflexo da disfunção astroglial ou da barreira hematoencefálica. MÉTODOS: Pesquisa de publicações no PubMed até o dia 15 de junho de 2011 visando estabelecer potenciais ligações entre a proteína S100B e as hipóteses correntes da esquizofrenia. RESULTADOS: A S100B está potencialmente associada com as hipóteses dopaminérgica e glutamatérgica. O aumento da expressão de S100B tem sido detectado em astrócitos corticais em casos de esquizofrenia paranoide, enquanto se observa uma redução da expressão em oligodendrócitos na esquizofrenia residual, dando suporte à hipótese glial. Recentemente, a hipótese da neuroinflamação da esquizofrenia tem recebido atenção crescente. Nesse sentido, a S100B pode funcionar como uma citocina secretada por células gliais, linfócitos CD8+ e células NK, levando à ativação de monócitos e microglia. Além disso, a S100B apresenta propriedades do tipo adipocina e pode estar desregulada na esquizofrenia, devido a distúrbios da sinalização de insulina, levando ao aumento da liberação de S100B e ácidos graxos do tecido adiposo. CONCLUSÃO: A expressão de S100B em diferentes tipos celulares está envolvida em muitos processos regulatórios. Atualmente, não pode ser respondido qual mecanismo relacionado à esquizofrenia é o mais importante

Scientific evidence for increased S100B concentrations in the peripheral blood of acutely ill schizophrenia patients is consistent. In the past, this finding was mainly considered to reflect astroglial or blood-brain barrier dysfunction. METHODS: Using Entrez, PubMed was searched for articles published on or before June 15, 2011, including electronic early release publications, in order to determine other potential links between S100B and current hypotheses for schizophrenia. RESULTS: S100B is potentially associated with the dopamine and glutamate hypotheses. Supporting the glial hypothesis, an increased expression of S100B has been detected in cortical astrocytes of paranoid schizophrenia cases, while decreased oligodendrocytic expression has been observed in residual schizophrenia. Recently, the neuroinflammation hypothesis of schizophrenia has gained attention. S100B may act as a cytokine after secretion from glial cells, CD8+ lymphocytes and NK cells, activating monocytes and microglial cells. Moreover, S100B exhibits adipokine-like properties and may be dysregulated in schizophrenia due to disturbances in insulin signaling, leading to the increased release of S100B and free fatty acids from adipose tissue. DISCUSSION: Dysregulation of pathways related to S100B appears to play a role in schizophrenia. However, S100B is expressed in different cell types and is involved in many regulatory processes. Currently, "the most important" mechanism related to schizophrenia cannot be determined