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.

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.

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 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.

Acute disseminated encephalomyelitis in a 5-month old infant

This article reports on an 5-month-old infant who was admitted to our hospital for prolonged fever, focal status epilepticus and encephalopathy. Brain magnetic resonance imaging [MRI] demonstrated a single hyperintense lesion in right putamen in T2-weighted images. A diagnosis of acute disseminated encephalomyelitis was made based on the clinical features, treatment response and clinical course. An executive literature review revealed a few cases under the age of one year .This patient is the youngest are who is reported from Iran

potential diagnostic value of diffusion-weighted imaging in acute disseminating encephalomyelitis

Acute disseminating encephalomyelitis [ADEM] is a treatable inflammatory, demyelinating disorder of the central nervous system. Early application of steroids has been shown to reduce morbidity, therefore, early diagnosis is highly desirable. Magnetic resonance imaging [MRI] is the imaging modality of choice for establishing the diagnosis along with the clinical presentation. The aim of this report is to show the potential diagnostic value of advanced MR techniques such as diffusion-weighted imaging [DWI], which has been found to add to the diagnostic power of MRI in the setting of demyelinating disorder, even in the absence of contrast enhancement. We report a case of ADEM in an 11-year-old boy revealing high signal intensity changes on DWI indicating elevated diffusion

Acute combined demyelination of CNS and PNS: a case report

Acute disseminated encephalomyelitis [ADEM] and Guillain-Barre syndrome [GBS] are both para infectious demyelinating disorders. While ADEM almost always affects the CNS, GBS affects the PNS. The combined demyelinating process - demyelination of both upper motor neuron [UMN] and lower motor neuron [LMN] - occurs very rarely. Here we report a case of severe combined peripheral and central demyelination, in which the former disorder was preceded by the latter

Acute disseminated encephalomyelitis in an adult patient. magnetic resonance and diffusion-weighted imaging findings

Acute disseminated encephalomyelitis ADEM is an uncommon inflammatory disease of the central nervous system and can be defined strictly as scattered focal or multifocal disseminated inflammation of brain or spinal cord, or both. An ADEM usually reveals patchy demyelinated lesions with a high signal on T2-weighted sequences. Here, we report a case of a 39-year-old man with ADEM. Echo-planar trace diffusion magnetic resonance imaging revealed high signal intensity changes at the lesion sites on b=1000 s/mm2 images, initially suggesting restricted diffusion. On corresponding apparent diffusion coefficient ADC maps, however, the lesions have a high signal intensity and high ADC values, compared with the normal white matter. This was consistent with the presence of elevated diffusion, and hence, vasogenic edema