Concurrencia entre el síndrome de Guillain-Barré y púrpura trombocitopénica inmune posiblemente inducidos por COVID-19 prolongado / Concurrence between Guillain-Barré syndrome and immune thrombocytopenic purpura possibly induced by long COVID-19

RESUMEN Durante la infección aguda por el SARVS-CoV-2 se produce una desregulación del sistema inmune que puede durar hasta ocho meses después de controlado el cuadro agudo. Esto, sumado a otros factores, posiblemente este asociado con un aumento del riesgo de aparición y concurrencia de enfermedades autoinmunes. La aparición simultanea del síndrome de Guillain-Barré (SGB) y púrpura trombocitopénica (PTI) se ha reportado poco en la literatura, y el SGB raramente se asocia con otra enfermedad autoinmune. Presentamos el caso de un varón que luego de un mes de tener un cuadro agudo de COVID-19 moderado, presentó concurrentemente SGB y PTI con respuesta adecuada al tratamiento.

ABSTRACT During acute SARS-CoV-2 infection, there is persistent deregulation of the immune system that can last up to 8 months after the acute condition is controlled. This, added to other factors, is possibly associated with an increased risk of the appearance and concurrence of autoimmune diseases. The simultaneous occurrence of GBS and ITP has been rarely reported in the literature, and GBS is rarely associated with another autoimmune disease. We present the case of a man who, one month after his recovery from acute moderate COVID-19, presented concurrent GBS and ITP with an adequate response to treatment.

Balo's concentric lesions with concurrent features of Schilder's disease in relapsing multiple sclerosis: neuropathological findings

Atypical inflammatory demyelinating syndromes are rare neurological diseases that differ from multiple sclerosis (MS), owing to unusual clinicoradiological and pathological findings, and poor responses to treatment. The distinction between them and the criteria for their diagnoses are poorly defined due to the lack of advanced research studies. Balo's concentric sclerosis (BCS) and Schilder's disease (SD) are two of these syndromes and can present as monophasic or in association with chronic MS. Both variants are difficult to distinguish when they present in acute stages. We describe an autopsy case of middle-aged female with a chronic history of MS newly relapsed with atypical demyelinating lesions, which showed concurrent features of BCS and SD. We also describe the neuropathological findings, and discuss the overlapping features between these two variants.

Hemianopsia homônima como síndrome clínica isolada com alto potencial deconversão para esclerose múltipla / Homonymous hemianopia as an isolated clinical syndrome with high potential for conversion to multiple sclerosis

Introdução: A hemianopsia homônima ocorre apenas na presença de lesão retroquiasmática, sendo uma rara apresentação de doença desmielinizante. Objetivo: Relatar um caso raro de hemianopsia homônima como manifestação inicial de síndrome clinicamente isolada. Método: Foi realizada uma revisão de 809 prontuários médicos de pacientes com esclerose múltipla (EM) tratados no Hospital da Lagoa (Rio de Janeiro) entre 1995 e 2011, para identificação de casos de hemianopsiahomônima como manifestação inicial da doença. Relato de caso: Paciente do sexo feminino, 48 anos, apresentou em agosto de 2011 quadro de hemianopsia homônima esquerda incongruente associada à lesão em topografia do trato óptico direito, evidenciada na RM de crânio, que também revelou lesões periventriculares e em substância branca subcortical, compatíveis com doença desmielinizante. O exame do líquido cefalorraquidiano (LCR) revelou hiperproteinemia leve com síntese intratecal de IgG e IgM, e o estudo do potencial visual evocado mostrou comprometimento parcial das vias ópticas bilateralmente. Concluído o diagnóstico de síndrome clinicamente isolada, a paciente foi submetida à pulsoterapia com metilprednisolona, com remissão das queixas visuais e melhora acentuada do campo visual no segundo exame realizado. O diagnóstico de EM foi concluído em dezembro de 2011, com o resultado da segunda RM, que revelou redução no tamanho da lesão em topografia do trato óptico direito e persistência das lesões focais periventriculares e subcorticais, com o surgimento de novas lesões frontais captantes de contraste. Conclusão: Embora a neurite óptica seja a manifestação ocular mais frequente da síndrome clinicamente isolada, deve-se estar atento a outras formas atípicas de apresentação para que se possa fazer um diagnóstico precoce. Os defeitos de campo visual na EM geralmente têm bom prognóstico com o tratamento adequado...

Introduction: Homonymous hemianopia occurs only in the presenceof retrochiasmatic injury, being a rare presentation of demyelinatingdisease. Objective: To report a rare case of homonymoushemianopia as the initial manifestation of clinically isolated syndrome.Method: We conducted a review of medical records of 809 patientswith multiple sclerosis (MS) treated at Hospital da Lagoa (Rio de Janeiro) between 1995 and 2011, being found only one case of homonymous hemianopia as the initial manifestation of the disease. Case report: Female patient, 48 years old, presented in August 2011 incongruous left homonymous hemianopia associated with lesion in topography of the right optic tract evidenced in MRI, which also revealed lesions in periventricular and subcortical white matter, consistent with demyelinating disease. CSF revealed mild hyperproteinemia with intrathecal synthesis of IgG and IgM, and visual evoked potential study showed partial compromise of the optic pathways bilaterally. Completed the diagnostic of clinically isolated syndrome, the patient underwent pulse therapy with methylprednisolone, with remission of visual complaints and marked improvement of the visual in the second examination performed. The diagnosis of MS was completed in December 2011 with the result of the second MRI, which revealed a reduction in the lesion size in the right optic tract topography and persistence of periventricular and subcortical focal lesions, with theemergence of new frontal lesions uptake of contrast. Conclusion:Although optic neuritis is the most common ocular manifestation ofclinically isolated syndrome, we should be mindful of other atypicalforms of presentation so that we can make an early diagnosis. Thevisual defects in MS usually have a good prognosis with appropriatetreatment...

O legado dos exames post-mortem para o estudo da relação entre forma clínica e substrato patológico na esclerose múltipla. Uma revisão sobre a anatomopatologia da doença / The legacy of post-mortem examination for the study of the relation between the clinical form and the pathological substrate in multiple sclerosis. A review on the anatomopathology of the disease

Após a dissecção de cérebro de uma paciente em 1868, Charcot definiu uma evidência histopatológica mais assertiva para a esclerose múltipla (EM): "sclerose en plaque". Entretanto, mais de um século depois, poucos estudos examinando o substrato patológico específico de fenótipos clínicos diferentes da EM são encontrados na literatura. O objetivo deste estudo é uma revisão da literatura sobre achados post-mortem (autopsia, exame histopatológico e técnicas imuno-histoquímicas) em pacientes com EM. Utilizando os termos "autopsy", "necropsy", "pathology", "post-mortem" e "multiple sclerosis", a pesquisa foi desenvolvida sobre a literatura e recursos presentes no MEDLINE no período janeiro 1990 a agosto 2012. Artigos relevantes baseados em análise macro/microscópica das lesões da EM e o uso de técnicas imuno-histoquímicas (marcadores imunológicos e neurobiológicos) foram revistos. Tratados de patologia cirúrgica e neuropatologia em suas últimas edições foram também consultados. Além dos estudos no início dos anos 2000 que identificaram padrões diferentes de desmielinização em casos de autópsia, considerando a perda de mielina, a geografia e extensão das lesões, a destruição dos oligodendrócitos e a evidência do dano imunopatológico, estudos mais detalhados e baseados em aspectos anatomopatológicos e implicações patogênicas são raros. A maioria destes poucos e específicos estudos reportam que as lesões da EM tipicamente aparecem na substância branca, mas são também abundantes na substância cinza, heterogeneidade de lesões inter-paciente e homogeneidade intra-paciente, graus diferentes para perda de mielina e estágios de atividade, foco de atividade inflamatória que origina gliose fibrilar, distrofia de oligodendrócitos e densidade axonal central diminuída. Desmielinização é um importante indicador de progressão clínica e a remielinização pode ser incompleta ou decresce com a cronicidade da doença. A importância das lesões na substância branca de aparência normal e na substância cinzenta tem sido cada vez mais reconhecida em recentes estudos com técnicas imuno-histoquímicas. Não há ainda um consenso se as diferenças entre as formas clínicas são fundamentalmente quantitativas ou qualitativas em relação ao substrato patológico e mais estudos sobre autopsias utilizando exame histopatológico e técnicas modernas de imuno-histoquímica são necessários para dirimir esta questão. Um melhor entendimento sobre a heterogeneidade das lesões da esclerose múltipla proporcionará o desenvolvimento de métodos terapêuticos mais direcionados e eficazes.

After dissection of a female brain in 1868, Charcot outlined a more assertive histopathological evidence of Multiple Sclerosis: "sclerose en plaque". However, more than a century later, very few studies examining the specific underlying pathology of a defined MS clinical phenotype are found in literature. The purpose of this study is to provide a literature review of post-mortem findings (histopathology and immunohistochemical techniques) in MS patients. The literature in MEDLINE was searched from January 1990 to August 2012 using the terms "autopsy", "necropsy", "pathology", "postmortem" and "multiple sclerosis". Relevant papers based on macroscopic/microscopic analysis of the MS lesions and the use of broad spectrum of immunological and neurobiological markers (immunohistochemistry) were reviewed. Textbooks of Surgical Pathology and Neuropathology in latest editions were also consulted.Besides the studies in the early 2000s that identified different patterns of demyelination in autopsy cases, consider the myelin impairment, the geography and extension of lesions, the oligodendrocyte destruction and the evidence of immunopathological damage, more detailed studies based on anatomopathological aspects and pathogenic implications are rare. Most of these few specific studies reported that MS lesions typically appear in the white matter, but are also abundant in grey matter, inter-patient lesions heterogeneity with intra-patient homogeneity, different degree of myelin loss and stage of activity, focus of inflammatory activity that gives way to fibrillary gliosis, oligodendrocyte dystrophy and decreased central axonal density. Demyelination is an important pathological correlate of clinical progression and remyelination could be incomplete or decreases with disease chronicity. The importance of healthy-appearing white matter damage and grey matter demyelination has been increasingly recognized in recent studies using immunohistochemical techniques. There is still no consensus on whether the differences between the clinical forms of MS are fundamentally quantitative or qualitative in relation to the pathological substrate, and more detailed studies with data on autopsies is required to resolve this issue. A better understanding of the pathogenetic heterogeneity of MS lesions will lead the development of more effective treatment methods.

Remielinización total en un paciente con diagnóstico de Esclerosis Múltiple remitente recurrente en tratamiento con Interferón beta 1a / Total remyelination in a patient with relapsing remitting Multiple Sclerosis in treatment with Interferon beta 1a

INTRODUCCIÓN: La Esclerosis Múltiple es una enfermedad crónica desmielinizante, de etiología desconocida, que afecta al sistema nervioso central. Aqueja principalmente a mujeres entre 20 y 40 años, siendo una de las principales causas de discapacidad en población joven. Ocurre por un proceso inflamatorio autoinmune en la sustancia blanca del sistema nervioso central, generando lesiones desmielinizantes que son causantes de la sintomatología. Su forma de presentación clínica es variable, siendo la más frecuente la forma Remitente Recurrente, que se caracteriza por recuperaciones entre los episodios de reagudización, que en la mayoría de los casos con son completas. PRESENTACIÓN DEL CASO: Paciente de 21 años, sexo femenino, con diagnóstico de esclerosis múltiple remitente recurrente, que en control médico, luego de seis meses desde confirmado el diagnóstico e iniciado el tratamiento con Interferón beta 1a y estando asintomática, presenta remielinización total de todas las lesiones objetivado a través una resonancia nuclear magnética sin hallazgos patológicos. DISCUSIÓN: La remielinización de las lesiones, causante de la remisión de los síntomas, suele ser parcial y con mielina más delgada, la que se identifica en la resonancia nuclear magnética como “placas de sombra”. La remielinización total de todas las lesiones del sistema nervioso central ha sido escasamente descrita, presentándose sólo en un 2,6 por ciento de los pacientes, y plantea la presencia de factores intrínsecos aún desconocidos involucrados en la capacidad de regeneración de la mielina a nivel central, abriendo una nueva línea investigativa.

INTRODUCTION: Multiple Sclerosis is a chronic demyelinating disease, with unknown etiology, that affect the central nervous system. Mainly affects women between 20 and 40 years old, and is one of the most important causes of young people disability. It happens because an autoimmune inflammatory process in the white matters at the central nervous system, producing demyelinating lesions that causes the symptoms. The clinical presentation is changeable, the most frequent is the relapsing remitting form, it is marked by periods of improvement between worsening ones, which in most cases is not complete. CASE REPORT: Female, 21 years old, with the diagnoses of relapsing-remitting multiple sclerosis, that in a medical control, after six months since the diagnosis confirmation and the beginning of the treatment with interferon beta 1a and without symptoms, has a total remyelination of the injuries at the central nervous system, without pathological evidence at the magnetic resonance imaging. DISCUSSION: The remyelination of the injuries, that cause the remission of the symptoms, is usually partial with lower quality myelin, which is thinner and is identify by magnetic resonance imaging as “shadow plaques”. The total remyelination of all the injuries at the central nervous system is scantily reported, only in 2.6 percent of the patients, and propose that inherent factors are involve at the myelin regeneration process, opening a new investigative line.

Neuromielitis óptica tratada inicialmente como esclerosis múltiple: a propósito de un caso / Neuromyelitis optica initially treated as multiple sclerosis: a propos a case

Introducción: El síndrome de Devic o neuromielitis óptica (NMO) es una entidad clínica infrecuente autoinmune, desmielinizante e inflamatoria que se caracteriza por la presencia de hallazgos clínicos, imagenológicos y de laboratorio que evidencian neuritis óptica, mielitis aguda con lesión longitudinal de más de tres segmentos medulares y seropositividad para anticuerpos IgG específicos para el canal de acuaporina 4. Caso: Presentamos el caso de una mujer de 28 años con diagnóstico inicial de Esclerosis múltiple de hace 14 meses, quien consulta al servicio de urgencias del Hospital Universitario San Jorge de Pereira por disminución progresiva de la fuerza en miembros inferiores y retención urinaria con cinco días de evolución. Como antecedentes refiere neuritis óptica bilateral en tratamiento con Interferón Beta, con pobre mejoría clínica y corticoide parenteral para los cuadros agudos. Se realiza resonancia magnética de columna vertebral que reporta columna lumbar sin alteraciones y columna dorsal con mielopatía en los segmentos T5-T8, posible desmielinización. Cuadro hemático, química sanguínea, Proteína C Reactiva, complemento C3 y C4 dentro de los rangos normales. Discusión: La presentación aislada de neuritis óptica como debut en un cuadro clínico nos lleva a sospechar inicialmente en una enfermedad desmielinizante tipo esclerosis múltiple, lo que puede alterar el manejo inicial de los pacientes con neuromielitis óptica de base.

Background: Devic’s syndrome or neuromyelitis optica (NMO) is an autoimmune, inflammatory and demyelinating uncommon clinical entity characterized by the presence of clinical, imagining and laboratory evidence of optic neuritis, acute myelitis with longitudinal injury in more than three spinal segments and finally, NMO IgG seropositive for antibodies specific for the aquaporin channel 4. Case: We report a 28 years old woman diagnosed with multiple sclerosis 14 months ago, who consulted to emergency of Hospital Universitario San Jorge from Pereira by progressive reduction of strength in lower extremities and unrinary retention with duration of five days. She had a history of bilateral optic neuritis in treatment with interferon Beta 1-B, with poor clinical improvement, and parenteral corticosteroid for acute symptoms. Is performed a spinal Magnetic Resonance Imaging (MRI) reported a lumbar spine without changes and a dorsal spine with myelopathy in segments T5-T8, possible demyelinitation. Blood count, blood chemistry, C Reactive Protein, complement C3 and C4 within normal ranges. Discussion: The presentation of isolated optic neuritis as a clinical debut leads us to suspect initially in a demyelinating disease, multiple sclerosis type which can alter the initial management of patients with NMO.

Esclerosis múltiple en pacientes pediátricos: fisiopatología, diagnóstico y manejo / Pediatric multiple sclerosis: pathophysiology, diagnosis, and management

Objetivo: Realizar una revisión acerca de la esclerosis múltiple en pacientes pediátricos, haciendo énfasis en los factores fisiopatológicos, los métodos diagnósticos, los principales diagnósticos diferenciales, el tratamiento y el pronóstico, para, de esta forma, lograr suministrar conocimientos claves y actualizados sobre esta patología. Métodos: La búsqueda de artículos se realizó en las bases de datos PubMed y Scopus, introduciendo las palabras clave “multiple sclerosis”, “children”, “pediatric multiple sclerosis”, “pathophysiology”, “diagnosis”, “diagnostic criteria” y “treatment”. Los artículos seleccionados debían tener fecha de publicación posterior al año 2000, ser revisiones de tema o ensayos clínicos y estar publicados en los idiomas inglés o español. Resultados y Conclusiones: La esclerosis múltiple es una enfermedad con una tasa de incidencia de 2 a 4 por 100.000 habitantes en Colombia, de la cual la población pediátrica representa entre 2,7 a 5.0% de los casos. Las causas que se han atribuido a la enfermedad son múltiples, incluyendo factores ambientales como infecciones virales o bacterianas, exposición a humo de cigarrillo o deficiencia de vitamina D, entre otras, factores genéticos y factores inmunológicos. Su diagnóstico se basa en los hallazgos clínicos e imagenológicos, previa exclusión de enfermedades más comunes. Su tratamiento se divide en tres ejes: el tratamiento de eventos agudos, el tratamiento modificador de la enfermedad y el tratamiento sintomático. Para el primero los medicamentos de primera elección son los corticoides, para el segundo son los medicamentos inmunomoduladores como acetato de glatiramer, y para el tercero se debe realizar un enfoque multidisciplinario. Su pronóstico a largo plazo es variable y depende en alguna medida de la respuesta al tratamiento.

Objective: Review about Multiple Sclerosis in pediatric patients, emphasizing in pathophysiological factors, di agnos t i c met hods , mai n di f f er ent i al di agnos i s ,t r eat ment , and pr ognosi s, t hus pr ovi di ng cur r entknowledge about this pathology. Methods: Search of articles was made in PubMed and Scopus databases with key words “multiple sclerosis”, “children”, “pediatric mul t i pl e scl er osi s” , “ pat hophysi ol ogy” , “ di agnosi s” ,“diagnostic criteria”, and “treatment”. Selected articles must have a publication date after 2000, reviews or clinical trials, and have been published in English or Spanish languages. Results and Conclusions: Multiple sclerosis is a disease with an incidence of 2 to 4 per 100,000 habitants in Colombia, and pediatric population represents 2.7 to 5% of the cases. Multiple causes had been related to the disease, including environmental factors, such as viral or bacterial infections, tobacco smoke exposure or Vitamin D deficiency, among others; genetic and immunologic causes are exposed too. Diagnosis is based in clinical and imaging features, excluding previously other morecommon diseases. Management is divided in three axes: treatment of acute event, disease-modifying therapies and symptomatic therapy. The treatment of acute events is usually with corticoid therapy, for disease-modifying therapy the first election are immunomodulatory drugs, such as Glatiramer Acetate and for symptomatic therapy is necessary a mul t i di sci pl i nary approach. Long-termprognosis is variable and depends of treatment response. [Farfán JD, Espitia OM. Pediatric multiple sclerosis: pathophysiology, diagnosis, and management. MedUNAB 2011; 14:167-179].

Encefalomielitis aguda diseminada: [revisión] / Acute disseminated encephalomyelitis: [review]

La encefalomielitis aguda diseminada (EMAD) es la leucoencefalopatía adquirida de mayor presentación en la edad pediátrica, de naturaleza inflamatoria-autoinmune, generalmente monofásica, polisintomática, y asociada a compromiso del estado de conciencia. Frecuentemente es precedida por un proceso infeccioso o por una inmunización. Se revisó la literatura médica de los últimos años considerando los aspectos etiopatogénicos, clínicos, diagnósticos y terapéuticos. Se presentan los últimos criterios diagnósticos para la EMAD y sus formas recurrentes, así como la importancia de los diagnósticos diferenciales, entre ellos la Esclerosis Múltiple Pediátrica(EMP). Las imágenes de Resonancia Magnética (IRM) constituyen el estudio de elección para detectar lesiones desmielinizantes.

Acute disseminated encephalomyelitis (ADEM) is an acquired leucoencephalopathy, that occurs more frequently during childhood, of inflammatory autoimmune condition, usually monophasic, polysymptomatic and associated with sensory deterioration. It is a frequently preceded by infections or vaccinations. Recent medical literature was reviewed considering etiology, pathogenesis, clinical, diagnosis and treatment aspects. The current diagnostic criteria for ADEM, its variants and the relevance of differential diagnostics, like Pediatric Multiple Sclerosis (PMS) are included. Magnetic Resonance Imaging (MRI) is recommended to detect demyelination injuries. High doses of steroids are still the therapeutic alternative for ADEM.

Encefalomielitis aguda diseminada en pediatría: presentación de la casuística (2000-2008): Hospital de Niños J. M de Los Ríos, Caracas-Venezuela: (primer premio como póster con mejor contenido científico: LIV Congreso Nacional de Pediatría septiembre 2008): [revisión] / Acute disseminated encephalomyelitis in pediatrics: presentation of the series (2000-2008): HospitaL de Niños JM de Los Ríos Caracas-Venezuela: (first prize poster presentation LIV Congreso Nacional de Pediatria september 2008): [review]

La Encefalomielitis Aguda Diseminada (EMAD) es una leucoencefalopatía adquirida, de naturaleza inflamatoria, autoinmune, de presentación predominante en la edad pediátrica; generalmente es monofásica, polisintomática y con frecuente compromiso del estado de conciencia. No hay marcadores biológicos para su reconocimiento, por lo que la presentación clínica aunada a los hallazgos en la Resonancia Magnética cerebral son los que permiten realizar una adecuada aproximación diagnóstica. Su curso es generalmente favorable, sin embargo, el tratamiento con esteroides puede resultar beneficioso. Se presenta la experiencia con 16 pacientes atendidos en el Hospital de Niños “J.M de Los Ríos”, Caracas-Venezuela, en un periodo de 8 años (abril 2000-abril 2008), a la luz de los últimos criterios propuestos para la clasificación de la EMAD.

Acute Disseminated encephalomyelitis (ADEM) is an acquired inflammatory autoimmune nature leucoencephalopathy, which occurs more frequently in the pediatric age group. It is usually monophasic, polysymptomatic and with frequent deteriorating consciousness. There are no biological markers for diagnosis, therefore the clinical presentation coupled with findings in the brain Magnetic Resonance Imaging allow a proper diagnostic approach. Its course is generally favorable; however treatment with brain steroids can be beneficial. We present the experience with 16 patients treated at children’s Hospital “J.M de Los Ríos”, Caracas-Venezuela, in a period of 8 year (April 2000–April 2008), in the light of recent proposed criteria for the classification of ADEM.