Encefalomielite aguda disseminada com provável etiologia de Bartonella henselae / Acute disseminated encephalomyelitis with probable Bartonella henselae etiology

RESUMO A encefalomielite aguda disseminada é uma doença rara, aguda, inflamatória e desmielinizante do sistema nervoso central, presumivelmente associada, em mais de três quartos dos casos, a infecções (virais, bacterianas ou inespecíficas) e imunizações ou sem qualquer antecedente indentificável. Habitualmente, apresenta um curso monofásico com início de sintomas inespecíficos na fase prodrómica, podendo evoluir com alterações neurológicas multifocais e até à perda total da acuidade visual. Descrevemos o caso de um menino de 9 anos com quadro inicial de edema de papila causado por encefalomielite aguda disseminada devido a Bartonella henselae. Apesar da gravidade da doença, o diagnóstico e o tratamento precoce proporcionaram bons desfechos.

ABSTRACT Acute disseminated encephalomyelitis is a rare, acute, inflammatory, and demyelinating disease of the central nervous system. Presumably associated in more than three quarters of cases by infections (viral, bacterial, or nonspecific) and immunizations or without any identifiable antecedent. It usually presents a monophasic course with onset of nonspecific symptoms in the prodromal phase and may evolve with multifocal neurological changes and even visual acuity loss. We describe a case of a 9-year-old boy with an initial picture of papillary edema caused by acute disseminated encephalomyelitis due to Bartonella henselae. Despite the severity of the disease, early diagnosis and treatment provided good outcomes.

Acute Disseminated Encephalomyelitis in COVID-19: presentation of two cases and review of the literature / Encefalomielite disseminada aguda associada a COVID-19: relato de dois casos e revisão de literatura

ABSTRACT Background: Neurological manifestations of COVID-19 are still incompletely understood. Neurological manifestations may be due to direct viral effect on neurons and glial cells, to an immune-mediated response to the virus, or to a hypercoagulable state and associated endothelial damage, as well as to severe systemic disease with prolonged intensive care unit stay. Objective: To describe two patients with severe SARS-CoV-2 infection and delayed recovery of consciousness after sedation withdrawal, in whom MRI disclosed multifocal white matter brain lesions, compatible with the diagnosis of acute disseminated encephalomyelitis. Methods: Observational report of two cases of severe COVID-19 infection in patients from two tertiary hospitals in São Paulo, Brazil. Results: These patients underwent neurologic and systemic evaluation for delayed awakening after sedation withdrawal. MRI displayed multifocal centrum semiovale lesions, suggestive of demyelinating inflammation. Cerebrospinal fluid (CSF) polymerase chain reaction (PCR) for SARS-CoV-2 was negative in both cases. Conclusion: A recurrent pattern of multifocal white matter lesions can occur in COVID-19 patients, possibly associated with delayed awakening. Additional studies are necessary to elucidate the role of the viral infection and of inflammatory and immune-mediated associated changes in neurological manifestations of COVID-19.

RESUMO Introdução: As manifestações neurológicas causadas pela COVID-19 ainda não estão completamente elucidadas. O comprometimento neurológico pode decorrer de um efeito viral direto em neurônios ou em células gliais, a efeito imunomediado em resposta à infecção viral, ou de um efeito secundário a estados de hipercoagulabilidade e danos endoteliais, assim como decorrente de complicações sistêmicas graves relacionadas a cuidados intensivos prolongados na unidade de terapia intensiva. Objetivo: Descrever dois pacientes com recuperação tardia do nível de consciência após a retirada da sedação associados à infecção grave pelo SARS-CoV-2, que apresentaram lesões multifocais de substância branca, compatíveis com o diagnóstico de encefalomielite disseminada aguda. Métodos: Estudo observacional, com relato de dois casos de infecção grave pela COVID-19, em dois hospitais terciários na cidade de São Paulo, Brasil. Resultados: Os pacientes foram submetidos à investigação sistêmica e neurológica para avaliação de estado alterado de consciência após retirada de sedação. A ressonância magnética de crânio evidenciou lesões multifocais no centro semioval, sugestivos de processo inflamatório desmielinizante. Análise liquórica evidenciou PCR negativo para SARS-CoV-2 em ambos os casos. Conclusão: Lesões multifocais de substância branca podem ocorrer em pacientes com COVID-19, possivelmente associadas a estados alterados de consciência. Estudos adicionais são necessários para determinar o processo fisiopatológico da infecção viral e dos estados inflamatórios e imunomediados na gênese das manifestações neurológicas causadas pela COVID-19.

Encefalomielitis diseminada aguda / Acute disseminated encephalomyelitis

La encefalomielitis diseminada aguda es una enfermedad desmielinizante del sistema nervioso central que generalmente se presenta como un trastorno monofásico asociado con síntomas neurológicos multifocales y encefalopatía. Suele ser precedido de una infección viral generalmente de vía aérea superior y, con menor frecuencia, de antecedente vaccinal. Se presenta un paciente de 4 años de edad con ataxia, encefalopatía, descenso progresivo del Score de Glasgow, imágenes de Sistema Nervioso Central compatibles con encefalomielitis diseminada aguda y adecuada respuesta al pasaje de pulsos de metilprednisolona. El objetivo de la publicación es enfatizar la presentación proteiforme de esta enfermedad y mejorar el reconocimiento de la misma en forma oportuna

The Acute Disseminated Encephalomyelitis is a demyelinating disease of the central nervous system that usually presents itself as a single-phase disorder associated with encephalopathy and multifocal neurologic symptoms. It tends to be preceded by a viral infection usually upper airway and, less frequently, of vaccinal antecedent. We present the case of a 4 years old child with clinic of ataxia, encephalopathy with progressive decline in Glasgow, history of fever in previous days, images of Central Nervous System compatible with ADEM and appropriate response to pulses of methylprednisolone. We decided to present this case to emphasize the varied presentation of this disease and improve recognition of it in a timely manner

Acute disseminated encephalomyelitis (ADEM) associated with mosquito-borne diseases: Chikungunya virus X yellow fever immunization

Abstract Acute disseminated encephalomyelitis (ADEM) is a demyelinating autoimmune neuropathic condition characterized by extensive bilateral and confluent lesions in the cerebral white matter and cerebellum. The basal ganglia and gray matter may also be involved. In most cases, the symptoms are preceded by viral infection or vaccination. In this report, we present a case of ADEM associated with optic neuritis presenting alongside two potential triggering factors: chikungunya virus infection and yellow fever immunization.

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)

Treinamento do assoalho pélvico na retenção urinária decorrente de encefalomielite aguda disseminada / Pelvic floor muscle training in neurogenic bladder due to acute disseminated encephalomyelitis syndrome

A dengue pode desencadear manifestações neurológicas como a Síndrome de Encefalomielite Aguda Disseminada (ADEM), de caráter inflamatório, desmielinizante, que pode ter dentre as consequências déficits motores e sensitivos, neurite ótica e disfunções vesicais, como a retenção urinária, tornando o indivíduo dependente da realização do cateterismo vesical intermitente (CVI). Desta forma, o objetivo deste estudo é descrever o tratamento fisioterapêutico de uma paciente com retenção urinária, decorrente de Síndrome de ADEM pós-dengue. Paciente do sexo feminino, 52 anos, internada em hospital de média complexidade com diagnóstico de ADEM. Na avaliação inicial apresentava grau de força muscular 3 de membros inferiores e 4 de membros superiores, 2 de musculatura do assoalho pélvico (MAP) e retenção urinária, necessitando realizar CVI. Foram realizados 32 atendimentos com duração de uma hora, incluindo o treinamento do assoalho pélvico em diferentes posturas e eletroestimulação de superfície da MAP com equipamento da marca Ibramed. Paciente recebeu alta hospitalar com evidente melhora da força muscular global e sem necessidade de CVI, apresentando micção voluntária e sem resíduo pós-miccional, favorecendo a prevenção de agravos do trato urinário inferior e superior. (AU)

Dengue can trigger neurological manifestations such as Acute Disseminated Encephalomyelitis (ADEM), with inflammatory, demyelinating condition, which may have, among the consequences, motor and sensory deficits, optic neuritis and bladder dysfunctions, such as urinary retention, making the individual dependent on intermittent bladder catheterization (IBC). Therefore, the objective of this study was to describe the physiotherapeutic treatment of a patient with urinary retention, due to ADEM syndrome after dengue. A 52-year-old female patient admitted to a hospital of medium complexity with a diagnosis of ADEM. In the initial evaluation, she presented a degree 3 of muscular strength in the lower limbs and 4 in the upper limbs, 2 in pelvic floor musculature (PFM) and urinary retention, requiring IBC. We performed 32 one hour sessions, including pelvic floor muscle training in different positions and surface electrostimulation of PFM with Ibramed brand equipment. Patient was discharged with evident improvement of global muscle strength and without IBC, presenting voluntary voiding and without post void residual, favoring the prevention of lower and upper urinary tract injuries. (AU)

Enfermedades desmielinizantes en niños: Encefalomielitis diseminada aguda y esclerosis múltiple / Demyelinizing diseases in children. Acute disseminated encephalomyelitis and multiple sclerosis

Se revisan dos de las principales enfermedades desmielinizantes en niños, la encefalomielitis aguda diseminada (EAD) y la esclerosis múltiple (EM). Por sus características fisiopatológicas, etiologías probables, manifestaciones clínicas, diagnóstico, tratamiento, pronóstico, evolución, así como alteraciones atípicas que complican su diagnóstico; cuanto más pequeño es el paciente se necesita estudiar más, antes de llegar al diagnóstico. El Grupo Internacional de Estudio de Esclerosis Múltiple Pediátrica publicó las definiciones operativas para enfermedades desmielinizantes adquiridas del sistema nervioso central: la EAD es monofásica, polisintomática y con encefalopatía. Su duración es de hasta 3 meses, con síntomas fluctuantes y hallazgos en resonancia magnética. La EM se define como síndrome aislado monofocal o polifocal, sin encefalopatía. Actualmente se consideran dos enfermedades diferentes y distinguibles desde el inicio de los síntomas.

The two main demyelinating diseases in children are reviewed. Acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS). For its physiopathological characteristics, probable etiologies, clinical manifestations, diagnosis, treatment, prognosis, evolution, as well as atypical alterations that complicate its diagnosis, the smaller the child is, more study is needed before reaching the diagnosis. The International Study Group of Multiple Pediatric Sclerosis, published the operating definitions for demyelinating diseases acquired from the central nervous system in children: the ADEM is monophasic, polysymptomatic and with encephalopathy. Its duration is up to 3 months, with fluctuating symptoms and magnetic resonance findings. MS is an isolated monofocal or polyfocal syndrome, without encephalopathy. Currently, two different and distinguishable diseases are considered from the onset of symptoms.

Encefalomielitis aguda diseminada por Mycoplasma pneumoniae en un niño previamente sano / Acute disseminated encephalomyelitis due to Mycoplasma pneumoniae in a previously healthy boy

Se presenta el caso de un niño de 5 años sin antecedentes de enfermedad, que se internó en terapia intensiva por convulsiones tónico-clónicas focalizadas en la cara y en el hemicuerpo derecho, con documentación de temperatura axilar de 37,4°C. Se descartó la presencia de gérmenes comunes y la etiología viral a través de estudios de muestras de líquido cefalorraquídeo (LCR). Se sospechó la presencia de Mycoplasma pneumoniae por comprobarse inmunofluorescencia positiva en suero para anticuerpos de clase IgM. El diagnóstico se confirmó mediante la detección del ADN de dicho patógeno sobre la biopsia cerebral efectuada por el método de la reacción en cadena de la polimerasa (PCR) y una histología compatible con encefalomielitis aguda diseminada. El paciente recibió tratamiento con claritromicina y su evolución fue favorable. Al menos dentro de nuestros conocimientos, este es el primer caso en el que se detectó ADN de M. pneumoniae en una biopsia cerebral por el método de PCR.

We present here the case of a previously healthy 5 year-old boy hospitalized in an intensive care unit due to tonic-clonic seizures focused on the face and right side of the body, and axillary temperature of 37.4 °C. Common bacterial and viral etiology was ruled out through studies of cerebrospinal fluid (CSF) samples. Mycoplasma pneumoniae was suspected by a positive immunofluorescence serum test for IgM class antibodies. Finally, with a brain biopsy, M. pneumoniae was confirmed by polymerase chain reaction (PCR) and acute disseminated encephalomyelitis by pathological anatomy. The patient was treated with clarithromycin and had an uneventful evolution. At least to our knowledge, this is the first case in which M. pneumoniae DNA was detected by PCR in a brain biopsy.

Encefalomielitis diseminada aguda posinfecciosa en un paciente con sospecha de infección por virus dengue / Postinfectious acute disseminated encephalomyelitis in a patient with suspected dengue virus infection

Introducción: La infección por virus dengue es considerada una de las arbovirosis de mayor prevalencia en los países tropicales. La encefalomielitis diseminada aguda es un trastorno inflamatorio desmielinizante y multifocal que afecta al sistema nervioso central, de inicio agudo y curso clínico monofásico. El proceso inflamatorio se encuentra mediado por mecanismos inmunológicos y su relación con infecciones por el virus dengue aún no se establece con claridad. Objetivo: Describir un caso clínico con manifestaciones del sistema nervioso central después de una probable infección por el virus dengue. Presentación del caso: Paciente femenina de 50 años, con antecedentes de hipertensión arterial controlada. Quince días después de un cuadro de fiebre de 4 días de duración, que posiblemente fue por una infección por el virus dengue, comienza con síntomas y signos de afectación neurológica caracterizadas por ligera irritabilidad, dificultad para la concentración en una actividad específica de la vida cotidiana. Progresivamente se nota dificultad motora en el hemicuerpo izquierdo además de encontrarse agitada y distraída, motivo por el cual se decide su ingreso hospitalario. Se realiza el diagnóstico a través de los hallazgos en el examen físico, los estudios positivos de resonancia magnética nuclear y el resultado positivo de la IgM de dengue en sangre. Tanto la evolución clínica como la respuesta al tratamiento con esteroides fueron favorables. Conclusiones: El evento ocurrido en este caso sugiere que los facultativos deben tener presente el diagnóstico de encefalomielitis diseminada aguda en pacientes que han tenido infección previa o alta sospecha de esta por el virus dengue(AU)

Introduction: Dengue virus infection is one of the most prevalent arboviruses in tropical countries. Acute disseminated encephalomyelitis is an inflammatory demyelinating multifocal disorder affecting the central nervous system. Its onset is acute and its clinical course monophasic. The inflammatory process is mediated by immunological mechanisms, and its relationship to dengue virus infections is still not clear. Objective: Describe a clinical case of central nervous system manifestations after probable dengue virus infection. Case presentation: Female 50-year-old patient with a history of controlled hypertension. Fifteen days after a 4-day fever episode, possibly due to dengue virus infection, the patient starts presenting neurological signs and symptoms, such as slight irritability and difficulty to concentrate on a specific activity of daily living. The patient notices progressive motor difficulty in her left hemibody and she feels agitated and distracted. It is therefore decided for her to be hospitalized. A diagnosis is made based on physical examination findings, positive nuclear magnetic resonance studies, and the positive result of the dengue IgM blood test. Both the patient's clinical evolution and her response to treatment with steroids were favorable. Conclusions: The event herein described suggests that physicians should consider the diagnosis of acute disseminated encephalomyelitis in patients with previous infection or high suspicion of infection with dengue virus(AU)

Ensayo pictórico: diagnóstico diferencial radiológico en esclerosis múltiple / Pictory essay: radiological differential diagnosis of multiple sclerosis

La esclerosis múltiple (EM) es la enfermedad inflamatorio-desmielinizante del Sistema nervioso central más prevalente en adultos. La resonancia magnética (RM) juega un rol cada vez más importante en el estudio de esta patología, en especial en su diagnóstico precoz, por lo que la diferenciación imagenológica de variantes frecuentes e infrecuentes de EM con otras patologías de sustancia blanca que comprometen encéfalo y médula espinal es esencial. Mediante una revisión pictórica se ilustrarán características típicas en RM del compromiso por EM y de variantes menos habituales de lesión desmielinizante, y se ilustrarán hallazgos característicos de lesiones relacionadas a vasculopatías inflamatorias y no inflamatorias, encefalomielitis diseminada aguda (ADEM), neuromielitis óptica (NMO) y enfermedades vasculares de la médula espinal que pueden simular EM, con énfasis en el diagnóstico diferencial radiológico.

Multiple sclerosis (MS) is the most prevalent inflammatory-demyelinating disease of the central nervous system in adult population. Magnetic resonance imaging (MRI) has an increasingly important role, especially in early diagnosis, so the imaging differentiation of frequent and infrequent variants of MS with other white matter diseases of brain and spinal cord is essential. Through a pictorial essay we show typical MR features of MS and more infrequent variants of demyelinating lesions and illustrate characteristic imaging findings of inflammatory and non-inflammatory vasculopathies, acute disseminated encephalomyelitis (ADEM), neuromyelitis optica (NMO) and vascular diseases of spinal cord that may simulate MS, with emphasis on imaging differential diagnosis.

Enfermedades desmielinizantes / Demyelinating disorders

Las enfermedades desmielinizantes constituyen un grupo de afecciones de etiología autoinmune dirigida contra la mielina del sistema nervioso central. En muchos casos, el inicio del cuadro es precedido por una infección viral inespecífica. La esclerosis múltiple evoluciona con recaídas y remisiones con déficit neurológicos polifocales, siendo los más frecuentes la neuritis óptica, la mielitis transversa y el compromiso de tronco encefálico. Se caracteriza por lesiones hiperintensas que se observan en una resonancia magnética nuclear (RMN) en T2 y FLAIR peri-ventriculares y peri-callosas, cerebelo, tronco y médula espinal. La neuromielitis óptica se caracteriza por la presencia de neuritis óptica y mielitis transversa asociada a síndrome de área postrema y diencefálico. Las lesiones en RMN se distribuyen en los sectores ricos en acuaporina-4 (AQP-4): hipotálamo, peri tercer y cuarto ventrículo, nervios ópticos y médula espinal. Los anticuerpos anti AQP4 ayudan al diagnóstico aunque no son esenciales para el mismo. La encefalomielitis diseminada aguda es un cuadro clásicamente monofásico caracterizado por una encefalopatía aguda asociada a lesiones en RMN hiperintensas en T2 y FLAIR bilaterales, asimétricas, de gran tamaño y de bordes irregulares. En los tres casos, el líquido cefalorraquídeo (LCR) puede mostrar pleocitosis e hiperproteinorraquia. La presencia de bandas oligoclonales en LCR es característica de la esclerosis múltiple. En todos los casos, el tratamiento agudo incluye corticoides a altas dosis por vía endovenoso y en caso de no respuesta, plasmaféresis. Tanto la esclerosis múltiple como la neuromielitis óptica requieren tratamiento a largo plazo para evitar nuevas recaídas ya que se trata de enfermedades recurrentes.

Demyelinating diseases are a group of conditions of autoimmune etiology directed against the myelin of the central nervous system. In many cases, the onset of the illness is preceded by a nonspecific viral infection. Multiple sclerosis is a disease that evolves with relapses and remissions with polyfocal neurological deficits, being the most frequent optic neuritis, transverse myelitis and encephalic trunk involvement. Typically, magnetic resonance image (MRI) shows peri-ventricular, peri-callosal, cerebellum, brain stem and spinal cord hyperintensive lesions in T2 and FLAIR weighted images. Optic neuromyelitis is characterized by the presence of optic neuritis and transverse myelitis associated with the postrema and diencephalic area syndrome. MRI lesions are distributed in sectors rich with aquaporine-4 channels (AQP-4): hypothalamus, third and fourth ventricle, optic nerves and spinal cord. Finding anti AQP4 antibodies is useful for the diagnosis although they are not essential for it. Acute disseminated encephalomyelitis is typically a monophasic condition characterized by acute encephalopathy associated with hyperintense MRI large, bilateral and irregular asymmetric lesion in T2 and FLAIR weighted images. In all three cases, cerebral spine fluid (CSF) can show pleocytosis and hyperproteinorrachia. The presence of oligoclonal bands in CSF is characteristic of multiple sclerosis. In all cases, acute treatment includes high dose intravenous corticosteroids and plasmapheresis in non-responsive cases. Both multiple sclerosis and optic neuromyelitis require long-term treatment to prevent relapse and recurrent diseases.

Potential role of dengue virus, chikungunya virus and Zika virus in neurological diseases

This study showed that laboratory markers of recent infection by dengue, Zika or chikungunya arboviruses were detected in the biological samples of approximately one-third of patients with encephalitis, myelitis, encephalomyelitis or Guillain-Barré syndrome, in a surveillance programme in Piauí state, Brazil, between 2015-2016. Fever and myalgia had been associated with these cases. Since in non-tropical countries most infections or parainfectious diseases associated with the nervous system are attributed to herpesviruses, enteroviruses, and Campylobacter jejuni, the present findings indicate that in tropical countries, arboviruses may now play a more important role and reinforce the need for their surveillance and systematic investigation in the tropics.

Estudo do perfil de citocinas inflamatórias das doenças desmielinizantes adquiridas na faixa etária pediátrica em ambulatório especializado no estado do Rio de Janeiro / Study of the inflammatory cytokine profile of acquired demyelinating diseases in the pediatric age group in a specialized outpatient clinic in the state of Rio de Janeiro

O grupo de Doenças Desmielinizantes Adquiridas (DDA) acomete o Sistema Nervoso Central (SNC) com base imunopatológica com produção de anticorpos à bainha de mielina. O diagnóstico é baseado em critérios clínico-radiológicos, sendo importante a busca por novas tecnologias para melhores diagnóstico e terapêutica. A avaliação da resposta inflamatória pode ser preditiva do curso evolutivo, sendo pouco explorada em pediatria. A proposta foi avaliar parâmetros clínico-neurológicos e perfis imunológicos nas DDA pediátricas para identificar biomarcadores dos quatro subtipos de DDA: Encefalomielite Disseminada Aguda (ADEM), Esclerose Múltipla Pediátrica (EMP), Síndrome Clínica Isolada (CIS) e Espectro da Neuromielite Óptica (NMOSD). Foi realizado um estudo prospectivo, longitudinal com portadores de DDA com até 18 anos de idade no Ambulatório de Doenças Desmielinizantes do IFF no período de 2012 a 2016. Os pacientes foram submetidos a exame neurológico evolutivo, Ressonância Magnética (RM) e coleta de sangue para pesquisa de citocinas. Foram admitidos 30 pacientes com 12 exclusões e 3 perdas totalizando 15 pacientes avaliados. O diagnóstico mais encontrado foi ADEM seguido de EMP. Os painéis de citocinas foram comparados através de análise estatística e categorizados de acordo com as comparações. Os resultados foram descritos em gráficos Heatmap, Boxplot e árvore de decisões. Foi relatado um caso sobre a evolução do diagnóstico de CIS para EMP. O perfil de citocinas séricas foi realizado por análise de microarranjo líquido (Luminex) totalizando 64 amostras de sangue avaliadas. A coorte apresentou cinco pacientes ADEM, cinco EMP, dois CIS e três NMOSD. No relato de caso da paciente ALAPL, não foi encontrada sincronia temporal entre a alteração do perfil de citocinas, da RM e da avaliação neurológica concluindo que avaliações inflamatória e clínica não anteciparam eventos de desmielinização e evolução para EMP. A correlação entre dosagens de citocinas mostrou um padrão multifuncional, com a participação de moléculas associadas ao perfil inflamatório Th1, Th2, Th17, Treg, e expressão aumentada de quimiocinas e citocinas envolvidas com proliferação de diversos tipos celulares. O padrão inflamatório mais abrangente e polifuncional, com 20 citocinas significativamente mais expressas, foi entre a EMP comparadas à ADEM. Na análise de citocinas entre ADEM e MNOSD houve uma diferença estatisticamente significativa para IL-7, IL-10 e GM-CSF, com uma expressão maior nas amostras de NMOSD. Entre CIS e ADEM, apenas MIP-1b se apresentou com uma diferença estatística nos dois grupos. A IP-10 se mostrou diferencialmente expressa em EMP quando comparada a CIS. Entre EMP e NMOSD, encontramos a eotaxina aumentada em EMP. Foram criadas quatro árvores classificatórias para o diagnóstico de DDA, definindo o perfil mínimo de citocinas capazes de identificar cada tipo de DDA. Concluímos que do ponto de vista diagnóstico as citocinas IL-2, IL-7, IL-13, Basic-FGF, MIP-1b, VEGF, Eotaxina, IP-10 e TNF- seriam capazes de classificar todos os pacientes DDA em seus grupos específicos. Estudos multicêntricos que permitam aumentar o número de pacientes com DDA poderão auxiliar na validação dos achados desse trabalho e definir pontos de cortes mais precisos para cada nível de citocina sérica visando ao diagnóstico diferencial de DDA em pediatria.

The group of Acquired Demyelinating Diseases (DDA) affects the Central Nervous System (CNS) with immunopathological basis with production of antibodies to the myelin sheath. The diagnosis is based on clinical-radiological criteria, being important the search for new technologies for better diagnosis and therapeutics. The evaluation of the inflammatory response can be predictive of the evolutionary course, being little explored in pediatrics. The purpose of this study was to evaluate clinical and neurological parameters and immunological profiles in pediatric ADIs to identify biomarkers of the four ADD subtypes: Acute Disseminated Encephalomyelitis (ADEM), Pediatric Multiple Sclerosis (EMP), Isolated Clinical Syndrome (CIS) and Optical Neuromyelitis Spectrum ). A prospective, longitudinal study was conducted with patients with ADD up to 18 years of age at the IFF Demyelinating Diseases Clinic in the period from 2012 to 2016. The patients were submitted to evolutionary neurological examination, EDSS, Magnetic Resonance (MRI) and collection to detect cytokines. Thirty patients with 12 exclusions and 3 losses totaling 15 patients were admitted. The most common diagnosis was ADEM followed by EMP. The cytokine panels were compared between the DDAs by statistical analysis and categorized according to the comparisons. The results were described in Heatmap, Boxplot and decision tree charts. A case has been reported on the evolution of the diagnosis of CIS to PMS. Serum cytokine profile was performed by liquid microarray analysis (Luminex), totalizing 64 blood samples. The cohort presented five ADEM, five EMP, two CIS and three NMOSD patients. In the case report of the ALAPL patient, no temporal synchrony was found between the alteration of the cytokine profile, MRI and neurological evaluation, concluding that inflammatory profile evaluations and clinical examination did not anticipate events of demyelination and evolution to PMS. The correlation between cytokine dosages and ADI in pediatrics showed a multifunctional pattern with the participation of molecules associated with the inflammatory profile Th1, Th2, Th17, Treg, and increased expression of chemokines and cytokines involved with proliferation of several cell types. The most comprehensive and multifunctional inflammatory pattern, with 20 significantly more expressed cytokines, was seen among PMS compared to ADEM. In the analysis of cytokines between ADEM and MNOSD there was a statistically significant difference for IL-7, IL-10 and GM-CSF, with a greater expression in the samples of patients with NMOSD. Between CIS and ADEM, only MIP-1b presented a statistical difference in the two groups. IP-10 was differentially expressed in EMP when compared to CIS patients. Among patients with EMP and NMOSD, we found increased eotaxin in EMP. Four classification trees were created for the diagnosis of ADI, defining the minimum profile of cytokines capable of identifying each type of ADI. We conclude that IL-2, IL-7, IL-13, Basic-FGF, MIP-1b, VEGF, Eotaxin, IP-10 and TNF-γ could be classified as diagnostic groups. Multicentric studies that allow an increase in the number of patients with ADD can help to validate the findings of this study and define more precise cutoff points for each level of serum cytokine aiming at the differential diagnosis of AD in pediatrics.

Complicaciones neurológicas del virus chikunguya y dengue / Neurological complications of chikungunya and dengue virus

Resumen Los virus chikungunya (CHIKV) y dengue (DENV) son arbovirus transmitidos por el mosquito Aedes. La infección por ambos virus es casi privativa de regiones tropicales y subtropicales , pero en los últimos años han aparecido casos en la mayoría de los países, lo que ha aumentado el interés en estos virus. En esta revisión se describe las manifestaciones neurológicas de CHIKV y DENV. Los cuadros neurológicos observados en pacientes infectados por estos virus son en la mayoría de los casos encefalitis y encefalopatía. También hay cuadros de mielitis y encefalomielitis aguda diseminada(ADEM) post infecciosas. Más infrecuentemente se observa compromiso periférico: síndrome de Guillain Barré(SGB) y mononeuritis. La miositis y la parálisis periódica se observan aunque raramente en la infección por DENV. El diagnóstico se realiza por serología Ig M específica o por detección de ARN viral en suero y LCR. El tratamiento es de sostén pues no hay tratamiento específico. Los pacientes con cuadros post infecciosos/inmunomediados se tratan con inmunoglobulina(IG) EV o plasmaféresis(SGB)y con metilprednisolona/IG en pacientes con ADEM. Es fundamental realizar el diagnóstico precoz de la infección por DENV y CHIKV para tratar a tiempo las complicaciones sistémicas y neurológicas, en especial las encefalitis y cuadros postinfecciosos.

Abstract Chikungunya (CHIKV) and dengue (DENV) viruses are arboviruses transmitted by the Aedes mosquito. Infection by both viruses is almost deprived of tropical and subtropical regions, but in recent years cases have appeared in most countries, which has increased the interest in these viruses. This review describes the neurological manifestations of CHIKV and DENV. The neurological pictures observed in patients infected by these viruses are in most cases encephalitis and encephalopathy. There are also post-infectious myelitis and disseminated acute encephalomyelitis (ADEM). Peripheral involvement is more rarely observed: Guillain Barré syndrome (GBS) and mononeuritis. Myositis and periodic paralysis are seen but rarely in DENV infection. The diagnosis is made by specific IgM serology or by detection of viral RNA in serum and CSF. The treatment is supportive as there is no specific treatment. Patients with post-infectious / immunomediated squares are treated with immunoglobulin (IG) EV or plasmapheresis (GBS) and with methylprednisolone / GI in patients with ADEM. Early diagnosis of infection by DENV and CHIKV is essential to treat systemic and neurological complications, especially encephalitis and postinfectious disease.

Encefalitis recurrente post vacuna influenza anual / Recurrent encephalitis following annual influenza vaccine: case report

Influenza vaccine is rarely associated with neurological adverse effects such as Guillain Barré syndrome, encephalitis or aseptic meningitis. We report the case of a male patient that presented two episodes of acute encephalitis in consecutive years, 16 and 20 days after his annual influenza vaccine shot, respectively. In both instances, patient required ICU admission and evolved with fast recovery and no sequels. The first episode was managed empirically as herpetic encephalitis but an extensive study was performed in the second episode without identifying any microorganism. Neuroimaging studies also discarded acute disseminated encephalomyelitis. Mild pleocytosis of mononuclear predominance was detected in both cases in CSF. Naranjo score punctuated 8 points indicating a probable causal relationship. Acute encephalitis is a rare adverse effect of influenza vaccine and occurs several days after immunization. It has a broad differential diagnosis, and appears to be of self-limited duration and associated with good prognosis.

La vacuna influenza en raras ocasiones se asocia a efectos adversos neurológicos tales como síndrome de Guillain Barré, encefalitis o meningitis aséptica, entre otros. Presentamos el caso clínico de un paciente de sexo masculino de 66 años que presentó dos episodios de encefalitis en años consecutivos, 16 y 20 días después de recibir la vacuna anual de influenza, respectivamente. En ambos casos requirió ingreso a UCI y evolucionó con una rápida recuperación y sin secuelas. El primer episodio fue manejado empíricamente como una encefalitis herpética y en el segundo se hizo un extenso estudio microbiológico que no identificó microorganismos. Los estudios de neuroimágenes descartaron una encefalomielitis aguda diseminada. En ambos casos se pesquisó pleocitosis de predominio mononuclear en el LCR. El score de Naranjo dio 8 puntos indicando una probable relación causal. La encefalitis aguda es un efecto adverso muy infrecuente tras la vacuna influenza y ocurre varios días después de la inmunización. Tiene un amplio diagnóstico diferencial, parece ser autolimitado y de buen pronóstico.

Encefalomielitis diseminada aguda / Acute disseminated encefalomielitis

Se presenta el caso de un paciente quien inicia con cuadro agudo de debilidad progresiva, afebril, considerando inicialmente, lesión de neurona inferior, clinicamente no compatible, se inicia el tratamiento empirico para infección de Sistema Nervioso Central (SNC), hasta que se descarta el mismo. Vacunando hacia un mes y diez días, clinicamente de lesión de neurona motora superior se realiza Resonancia magnética con imágenes compatibles con Enfefalomielitis Diseminada Aguda (EMDA), se inicia inmunoglobulinas con evolución satisfactoria.

Acute disseminated encephalomyelitis following inactivated influenza vaccination in the Brazilian Amazon: a case report

Here, we describe a case of acute disseminated encephalomyelitis (ADEM) that occurred during a plausible risk interval following inactivated influenza vaccination in a previously healthy 27-year-old man from Manaus, Brazil. He was treated with intravenous methylprednisolone and immunoglobulin. One-month follow-up revealed resolution of the brain lesions, but not of the spinal cord lesions. No recurrence or progression of the main neurological symptoms was observed. After two years of monitoring, the patient continues to experience weak lower limbs and urinary retention. Thus, we recommend that ADEM should be considered in a patient presenting with neurological symptoms after influenza vaccination.

Encefalomielitis aguda diseminada grave: Comunicación de un caso asociado a infección por virus parainfluenza 3 / Severe acute disseminated encephalomyelitis associated with parainfluenza 3 infection: Case report

Disseminated encephalomyelitis (ADEM) is an infrequent condition with considerable morbidity and mortality in adult patients. It requires a high level of suspicion and diagnosis emerges by gathering clinical information, laboratory exams and images studies. ADEM is related to an immunological phenomena occurring after a bacterial/viral infection or recent vaccination. Glucocorticoids are the first line treatment, reserving immunoglobulins and plasmapheresis to refractory cases. We report a male patient aged 25, with ADEM associated to parainfluenza 3 virus respiratory infection that required mechanical ventilation and that had a complete recovery only after plasmapheresis.

La encefalomielitis aguda diseminada es una enfermedad infrecuente pero de elevada morbi-mortalidad en pacientes adultos. Demanda una sospecha y diagnóstico precoz que requiere el concurso de información clínica, pruebas de laboratorio y estudio de imágenes. De sustrato inmunológico, se puede relacionar a una infección viral, bacteriana o inmunización reciente. Los glucocorticoides son el tratamiento de elección, mientras que la inmunoglobulina intravenosa y la plasmaféresis se reservan para casos refractarios. Se presenta el caso de una encefalomielitis aguda diseminada grave, en un paciente de sexo masculino de 25 años, asociado a una infección respiratoria por virus parainfluenza 3. Requirió conexión a ventilación mecánica y tuvo una respuesta completa con plasmaféresis.

Encefalomielitis aguda diseminada en el adulto Caso de asociación con infección por el virus de la hepatitis A / Acute disseminated encephalomyelitis in adults Association with infection by hepatitis A virus

Resumen La encefalomielitis aguda diseminada (ADEM) es una enfermedad desmielinizante monofásica, queusualmente sigue a una infección o vacunación, principalmente por el virus del sarampión, y ocurre principalmente en niños y adultos jóvenes. Su asociación con la infección por el virus de la hepatitis A es rara, y se halla poco documentada. Se presenta el caso de una paciente femenina de 53 años con ADEM e infección por hepatitis A. Se resalta la inclusión de la hepatitis A dentro del tamiz causal de pacientes adultos con ADEM. (Acta Med Colomb 2014; 39: 64-68).

Abstract Acute disseminated encephalomyelitis (ADEM) is a monophasic demyelinating disease that usually follows an infection or vaccination, mainly by the measles virus and occurring primarily in children and young adults. His association with infection by hepatitis A virus is rare, and is poorly documented. The case of a 53 years old female patient with ADEM and infection by hepatitis A is presented. The inclusion of hepatitis A within the causal screening of adult patients with ADEM is highlighted. (Acta Med Colomb 2014; 39: 64-68).