A propósito de un caso pediátrico de tuberculosis oftálmica y drogorresistencia / Presentation of a Pediatric Case of Ocular Tuberculosis and Drug Resistance

El compromiso ocular es una forma extrapulmonar de tuberculosis. Puede comprometer cualquier componente del sistema visual. Las manifestaciones oculares pueden ser causadas por una infección activa que invade el ojo o por una reacción inmunológica de hipersensibilidad retardada. Las presentaciones clínicas más comunes son uveítis anterior crónica, coroiditis y esclero-queratitis. A pesar de la existencia de herramientas moleculares altamente sensibles, arribar al diagnóstico de formas poco frecuentes o no pensadas como la TB ocular en un niño sigue siendo un gran reto y se basa en la presentación clínica, evaluación sistémica y la respuesta terapéutica. El tratamiento implica el uso de antifímicos y, muchas veces, esteroides. El objetivo fue presentar una forma de tuberculosis endoftálmica, pulmonar miliar y meníngea, en el marco de la drogorresistencia.

Eye engagement is an extrapulmonary form of tuberculosis. It can compromise any component of the visual system. Eye manifestations can be caused by an active infection that invades the eye or by a delayed hypersensitivity immune reaction. The most com mon clinical presentations are: chronic anterior uveitis, choroiditis and sclero-keratitis. Despite the existence of highly sensitive molecular tools, arriving at diagnosis in rare or undeceived ways with eye tuberculosis in a child remains a major challenge, based on clinical presentation, systemic evaluation and therapeutic response. Treatment involves the use of antiphymics and often steroids. The objective was to present a form of endophthalmic tuberculosis, miliary pulmonary and meningeal, in the framework of drug resistance.

Meningioma Meningoendotelial Associado à Tuberculose: um Relato de Caso / Tuberculosis-Associated Meningoendothelial Meningioma: a Case Report

O presente estudo relata um caso de coexistência entre um meningioma meningoendotelial associado a múltiplos granulomas epitelioides com focos de necrose caseosa, sendo possivelmente um dos primeiros casos relatados em imagens anatomopatológicas com imuno-histoquímica desta associação de um tumor com colonização pelo bacilo de Koch. Paciente de 79 anos, oligossintomática acompanhada por onze anos devido à lesão em tomografia sugestiva de meningioma, dá entrada em hospital terciário com história de crise convulsiva e dificuldade de falar. Após crises convulsivas recorrentes, foi indicada exérese tumoral, sendo observada em anatomopatológico a existência de múltiplos granulomas epitelioides com focos de necrose caseosa, sendo confirmada a presença de bacilos após aplicação da coloração de Ziehl-Neelsen e imuno-histoquímica. Observou-se a inexistência de sintomas e/ou achados laboratoriais/imaginológicos que demonstrassem sítio de colonização pelo bacilo. A maior vascularização desses tumores, a estase sanguínea e edema perilesional causado pela compressão das estruturas adjacentes e seu lento crescimento tornam os meningiomas ambientes propícios à colonização de bactérias, fungos, vírus e micobactérias. Além disso, compreende-se que os meningiomas possuem uma série de diagnósticos diferenciais clínico-radiológicos, sendo, muitas vezes, necessário o exame histopatológico e imuno- -histoquímico para a confirmação do diagnóstico.

This study reports a case of coexistence of a meningoendothelial meningioma associated with multiple epithelioid granulomas with foci of caseous necrosis, possibly one of the first cases reported in anatomopathological images with immunohistochemistry of this association of a tumor with colonization by Koch's bacillus. A 79-year-old patient, oligosymptomatic, followed for eleven years due to a tomography lesion suggestive of meningioma, was admitted to a tertiary hospital with a history of convulsive crisis and difficulty speaking. After recurrent convulsive crises, there was an indication for tumor excision, and the anatomopathological examination revealed multiple epithelioid granulomas with foci of caseous necrosis, confirming the presence of bacilli after the application of Ziehl-Neelsen staining and immunohistochemistry. No symptoms and/or laboratory/imaging findings demonstrated a site of colonization by the bacillus. The increased vascularity of these tumors, the blood stasis, and perilesional edema caused by compression of adjacent structures and their slow growth make meningiomas favorable environments for colonization by bacteria, fungi, viruses, and mycobacteria. Furthermore, it is understood that meningiomas have several clinical-radiological differential diagnoses, and histopathologic and immunohistochemical examinations are often necessary to confirm the diagnosis.

Experiencia en el diagnóstico de tuberculosis meníngea en un hospital de alta complejidad en Colombia / The experience of a tertiary care hospital in Colombia in the diagnosis of meningeal tuberculosis

Resumen Introducción: la tuberculosis es una de las enfermedades infecciosas de mayor distribución mundial y la tuberculosis meníngea es una de sus manifestaciones más devastadoras. Su diagnóstico y confirmación microbiológica no siempre es fácil. Objetivo: describir la experiencia en el diagnóstico de tuberculosis meníngea por pruebas moleculares comparado con cultivo, caracterizando las principales manifestaciones clínicas y determinar los factores asociados a mortalidad. Métodos: identificamos retrospectivamente a los pacientes adultos con diagnóstico de tuberculosis meníngea, mediante técnicas de pruebas moleculares y/o cultivo para M. tuberculosis, que ingresaron en nuestra institución entre enero de 2018 y marzo de 2020, se realizó un análisis estadístico descriptivo. Se excluyeron mujeres gestantes, pacientes que no contaran con prueba molecular para M. tuberculosis. Resultados: se obtuvo una muestra de 33 pacientes, los hallazgos más relevantes en el citoquímico de líquido cefalorraquídeo (LCR) fue la presencia de hipoglucorraquia, con una mediana de 34.2 mg/dL (RIQ 2.0-95.0 mg/dL) y de hiperproteinorraquia, con mediana de 265 mg/dL (RIQ 24.0-600 mg/dL). El resultado más significativo fue la presencia de proteína C reactiva elevada en suero en todos los casos, con una mediana de 53.3 mg/L (RIQ 22.9-89.6 mg/L) y neutrofilia en 75.8% (25). La mortalidad fue de 54.5% (18), la sensibilidad de la prueba molecular en LCR fue del 38.46% y el valor predictivo positivo de 58.82%. Conclusiones: el diagnóstico de TB meníngea sigue siendo todo un reto, aunque las pruebas moleculares pueden ayudar en el diagnóstico temprano, su sensibilidad es baja en formas extrapul-monares. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2115).

Abstract Introduction: tuberculosis is one of the most widely disseminated infectious diseases worldwide, and meningeal tuberculosis is one of its most devastating manifestations. Its diagnosis and microbiological confirmation is not always easy. Objective: to describe the experience in diagnosing meningeal tuberculosis through molecular tests compared to a culture, characterize the main clinical manifestations, and determine factors associated with mortality. Methods: we retrospectively identified adult patients diagnosed with meningeal tuberculosis through molecular and/or culture tests for M. tuberculosis who were admitted to our institution between January 2018 and March 2020. A descriptive analysis was performed. Pregnant women and patients who did not have a molecular test for M. tuberculosis were excluded. Results: a sample of 33 patients was obtained. The most relevant cerebrospinal fluid (CSF) cytochemical analysis findings were low glucose, with a median of 34.2 mg/dL (IQR 2.0-95.0 mg/ dL) and high protein, with a median of 265 mg/dL (IQR 24.0-600 mg/dL). The most significant result was elevated serum C-reactive protein in all cases, with a median of 53.3 mg/L (IQR 22.9 -89.6 mg/L) and neutrophilia in 75.8% (25). Mortality was 54.5% (18), the sensitivity of the CSF molecular test was 38.46% and the positive predictive value was 58.82%. Conclusions: the diagnosis of meningeal TB continues to be a challenge. While molecular tests can help provide an early diagnosis, their sensitivity is low in extrapulmonary forms. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2115).

Meningitis tuberculosa: un desafío diagnóstico en pediatría

Resumen La meningitis por Mycobacterium tuberculosis es infrecuente en pediatría y su diagnóstico definitivo representa un desafío clínico. Presentamos el caso de un lactante de dos años, que presentó un cuadro de meningitis crónica. Se logró el diagnóstico tras la sospecha imagenológica y la confirmación tras la búsqueda seriada del complejo M. tuberculosis por RPC en LCR y en biopsia de tejido cerebral. A pesar de sus complicaciones, el paciente respondió favorablemente al tratamiento antituberculoso. En Chile, la tuberculosis es infrecuente en niños y los síntomas son generalmente inespecíficos. Los hallazgos en RM cerebral asociados a alteraciones del LCR permiten sospechar el compromiso meníngeo precozmente. Se recomienda iniciar el tratamiento antituberculoso empírico ante la sospecha, ya que mejora el pronóstico. A pesar de los avances diagnósticos y terapéuticos, la meningitis tuberculosa sigue teniendo una alta tasa de complicaciones y un pronóstico ominoso.

Abstract Mycobacterium tuberculosis meningitis is rare in the pediatric population and its definitive diagnosis represents a clinical challenge. We present the case of a 2-year-old infant with chronic meningitis. Diagnosis was accomplished by suggestive radiological findings and serial search for M. tuberculosis complex by real-time polymerase chain reaction (qPCR) in cerebrospinal fluid (CSF) and in brain tissue. Despite the complications, the patient evolved favorably with the tuberculosis treatment. In Chile, tuberculosis is a rare disease in children and symptoms are generally nonspecific. Brain MRI findings associated with CSF alterations allow early suspicion of MTBC. Start of empirical antituberculosis treatment upon suspicion is recommended given it is associated with better prognosis. Despite diagnostic and therapeutic advances, MTBC continues to have a high complication rate and an ominous prognosis.

Uso de Quantiferon Gama no diagnóstico de meningite tuberculosa na criança: um relato de caso / Use of Quantiferon Gama in the diagnosis of meningeal tuberculosis in the child: a case report

Existem várias formas de infecção pelo bacilo M. tuberculosis, a meníngea é a mais grave delas. Por possuir efeitos colaterais graves e um longo tratamento o diagnóstico preciso é imprescindível para justificar o tratamento precoce da doença. Os métodos tradicionais de diagnóstico muitas vezes são insuficientes, sendo necessário o uso de exames mais modernos, que apesar de maior custo, apresentam menores índices de erros diagnósticos. Sendo assim, faz-se necessário o uso de exames com maior sensibilidade e especificidade, como o Quantiferon Gama. Relata-se o caso de um paciente masculino, 10 anos, admitido por cefaleia, sonolência, vômitos e rigidez de nuca. Exames tradicionais não ajudaram no diagnóstico, com necessidade de Quantiferon Gama (QTF-G) para diagnóstico definitivo de TB.

There are several forms of infection by the M. tuberculosis bacillus, the meningeal is the most serious of them. Because it has serious side effects and a long treatment, the precise diagnosis is essential to justify the early treatment of the disease. Traditional diagnostic methods are often insufficient, requiring the use of more modern tests, which, despite higher costs, have lower rates of diagnostic errors. Therefore, it is necessary to use tests with greater sensitivity and specificity, such as the Quantiferon Gamma. We report the case of a male patient, 10 years old, admitted for headache, drowsiness, vomiting and neck stiffness. Traditional exams did not help in the diagnosis, requiring Quantiferon Range (QTF-G) for diagnosis of TB.

Meningitis tuberculosa en un lactante: Reporte de caso y revisión de la literatura / Tuberculous meningitis in an infant: Case report and literature review

La tuberculosis (TBC) sigue siendo uno de los principales problemas de salud pública mundial. Actualmente es considerada una enfermedad reemergente, notificándose un aumento de la incidencia en niños. La meningitis tuberculosa (MT) es la forma más grave y temida de TBC en la infancia, siendo los niños menores los más susceptibles a desarrollarla. Un diagnóstico temprano y el tratamiento oportuno son esenciales para mejorar el pronóstico. Se debe iniciar el tratamiento empírico temprano de los casos sospechosos, sin esperar los resultados confirmatorios. Comunicamos el caso de un varón de 5 meses que presentó una MT con manifestaciones clínicas características y mala evolución. Se revisan los mecanismos fisiopatológicos subyacentes y las recomendaciones diagnósticas y terapéuticas actuales.

Tuberculosis (TB) remains a major public health problem worldwide. It is currently considered a re-emergent disease and its incidence in children is increasing. Tuberculous meningitis (TBM) is the most feared and deadly form of TB, being the younger children particularly susceptible to develop it. Early diagnosis and prompt treatment are essential to improve outcomes. Empirical treatment in suspected cases without confirmatory tests must be initiated. We analyze the case of a 5 month old infant with typical TBM and poor outcome. We review the underlying pathophysiology and the current diagnostic and management recommendations.

Tuberculosis extrapulmonar en el niño / Extrapulmonary tuberculosis in children

Pulmonary tuberculosis (TB) is the most common type of TB in children. Extrapulmonary tuberculosis is also prevalent (about 30-40 percent of cases) and it can occur in a variety of anatomical sites. This study presents a review of the literature on the main clinical manifestations of extrapulmonary tuberculosis in children, its diagnosis and treatment. At the end, some reflections on the importance of BCG for prevention are presented.

La tuberculosis (TB) pulmonar es el tipo más común de TB en niños. La tuberculosis extrapulmonar también es frecuente (alrededor de 30-40 por ciento de los casos) y se puede presentar en una gran variedad de sitios anatómicos. Se hace una revisión de la literatura sobre las principales manifestaciones clínicas extrapulmonares de la tuberculosis en niños, su diagnóstico y su tratamiento. Al final se hacen algunas reflexiones sobre la importancia de la BCG para su prevención.

Características clínicas y diagnósticas de tuberculosis meníngea en adultos, Bogotá (Colombia) / Clinical and diagnostic characteristics of meningeal tuberculosis in adults, Bogota (Colombia)

Introducción: La infección por Mycobacterium tuberculosis es una enfermedad con presencia mundial, cuya principal manifestación clínica es pulmonar; la tuberculosis meníngea es la segunda presentación extrapulmonar más frecuente después de la pleural y ocasiona alta morbimortalidad, pero un diagnóstico y tratamiento tempranos disminuyen estos desenlaces. Objetivo: Establecer las características clínicas de pacientes con tuberculosis meníngea en nuestras instituciones y la evaluación de los resultados obtenidos con los métodos diagnósticos disponibles. Materiales y métodos: Se realizó un estudio observacional descriptivo de corte transversal, mediante revisión de historias clínicas de pacientes con tuberculosis meníngea en el periodo 2003-2012, en dos instituciones de tercer y cuarto nivel de atención en Bogotá. Resultados: Se evaluaron 36 pacientes con tuberculosis meníngea, con edad media de 52,4 años, 63,8% sexo masculino y 16,6% coinfección con virus de inmunodeficiencia humana. La presentación clínica subaguda y crónica fue de 49,9%; 86,1% tuvieron cefalea; otros síntomas fueron: fiebre, rigidez nucal. En líquido cefalorraquídeo, todos tuvieron hiperproteinorraquia y 88,8% hipoglucorraquia. En estudios microbiológicos 71,8% tuvieron adenosin deaminasa positiva, 30,4% reacción en cadena de polimerasa positiva y 41,1% cultivo positivo. La hiponatremia fue de 36,1%. En neuroimágenes 18,7% presentaron hidrocefalia y 17,6% paquimeningitis. Conclusión: La tuberculosis meníngea representa hoy un reto diagnóstico, ya que no existe un método disponible con las características ideales de una prueba diagnóstica, debiendo considerarse las manifestaciones clínicas de meningitis subaguda o crónica y los hallazgos en líquido cefalorraquídeo primordiales para el diagnóstico e inicio temprano del tratamiento.

Introduction: Infection with Mycobacterium Tuberculosis is a worldwide disease whose main clinical manifestation is pulmonary, meningeal tuberculosis is the second most common extra-pulmonary presentation after pleural represents a high morbidity and mortality, early diagnosis and treatment reduces these outcomes. Objective: The aim of the study was to establish the clinical characteristics of patients with meningeal tuberculosis in our institutions and evaluation of the results obtained with the diagnostic methods available. Materials and methods:A descriptive cross-sectional study was conducted by reviewing the medical records of patients with meningeal tuberculosis; in the period between 2003-2012, two institutions third and fourth level of care in Bogotá. Results: 36 patients with meningeal tuberculosis, with a mean age of 52.4 years, 63.8% male, 16.6% coinfection with human immunodeficiency virus were evaluated. The subacute and chronic clinical presentation was 49.9%, 86.1% had headache, other symptoms were fever, neck rigidity, among others. In cerebrospinal fluid protein levels were 100%, 88.8% hypoglycorrhachia. 71.8% in microbiological studies were positive adenosine deaminase, 30.4% positive chain reaction polymerase and 41.1% positive culture. Hyponatremia was 36.1%. In neuroimaging, 18.7% and 17.6% had hydrocephalus Pachymeningitis. Conclusion: The meningeal tuberculosis today represents a diagnostic challenge because there is no method available with the ideal characteristics of a diagnostic test, having considered the clinical manifestations of subacute or chronic meningitis and cerebrospinal fluid findings in primary for diagnosis and initiation early treatment.

Intradural Extramedullary Tuberculoma of the Spinal Cord Following Tuberculous Meningitis

Intradural extramedullary tuberculoma of the spinal cord (IETSC) is an uncommon disease which can occurs secondary to tuberculous meningitis. A 31-year-old woman was diagnosed as tuberculous meningitis after mental disorientation. Her mentality was recovered after antituberculous therapy. After 7 months of antituberculous therapy, paraplegia has developed. Magnetic resonance imaging (MRI) revealed a mass lesion between the T1 and T12 spinal levels with arachnoid thickening which results in the development of tuberculoma. She received surgical resection of IETSC followed by antituberculous therapy and neurological function has been improved. The two years after surgical treatment, spinal MRI showed syringomyelia between T1 to L1. But, her neurological outcome was not aggravated.

Incidence of tuberculous meningitis in the State of Santa Catarina, Brazil

Introduction The aim of this study was to estimate the incidence of tuberculous meningitis in the State of Santa Catarina (SC), Brazil, during the period from 2001 to 2010. Methods Ecological, temporal, and descriptive methods were employed using data obtained from the Information System on Disease Notification (Sistema de Informação de Agravos de Notificação). Results One hundred sixteen reported cases of tuberculous meningitis occurred from 2001 to 2010, corresponding to 1.2% (0.2 cases/100,000 inhabitants) of all meningitis cases reported in SC. There was a predominance of new cases in males, corresponding to 56.9% of new cases (0.2 cases/100,000 inhabitants; males vs. females; p=0.374), in patients aged 20-39 years, corresponding to 52.6% of new cases (0.5 cases/100,000 inhabitants; 20-39 years versus others; p<0.001), and in urban areas, corresponding to 91.4% of new cases (0.2 cases/100,000 inhabitants; urban vs. rural; p=0.003). In 48.3% of cases, the outcome was death. Conclusions The incidence rate of tuberculous meningitis in SC has increased within the last decade, with the most affected population comprising young adult white males with an average education. Thus, tuberculous meningitis remains a serious disease, emphasizing the need for disease prevention with vaccination campaigns against tuberculosis, the development of faster and more accurate diagnostic methods, and the use of current epidemiological knowledge regarding the disease to facilitate the establishment of early treatment. .

Cerebrospinal fluid analysis in infectious diseases of the nervous system: when to ask, what to ask, what to expect / O exame do liquido cefalorraquidiano em doencas infecciosas do sistema nervoso: quando pedir, o que pedir, o que esperar

Cerebrospinal fluid (CSF) analysis very frequently makes the difference to the diagnosis, not only in relation to infections but also in other diseases of the nervous system such as inflammatory, demyelinating, neoplastic and degenerative diseases. The authors review some practical and important features of CSF analysis in infectious diseases of the nervous system, with regard to acute bacterial meningitis, herpetic meningoencephalitis, neurotuberculosis, neurocryptococcosis, neurocysticercosis and neurosyphilis.

O exame de líquido cefalorraquidiano (LCR) é frequentemente o elemento determinante para o diagnóstico não somente de infecções mas também de outras doenças do sistema nervoso, tais como doenças inflamatórias, desmielinizantes, neoplásicas e degenerativas. Os autores reveem alguns aspectos práticos e importantes quanto ao papel do exame de LCR em meningites bacterianas agudas, meningoencefalite herpética, neurotuberculose, neurocriptococose, neurocisticercose e neurossífilis.

Modelling of Cerebral Tuberculosis: Hope for Continuous Research in Solving the Enigma of the Bottom Billion’s Disease

Cerebral tuberculosis is a severe type of extrapulmonary disease that is highly predominant in children. It is thought that meningeal tuberculosis, the most common form of cerebral tuberculosis, begins with respiratory infection followed by early haematogenous dissemination to extrapulmonary sites involving the brain. Host genetic susceptibility factors and specific mycobacteria substrains could be involved in the development of this serious form of tuberculosis. In this editorial the different animal models of cerebral tuberculosis are commented, highlighting a recently described murine model in which BALB/c mice were infected by the intratracheal route with clinical isolates, which exhibited rapid dissemination and brain infection. These strains were isolated from the cerebrospinal fluid of patients with meningeal tuberculosis; they showed specific genotype and induced a peculiar immune response in the infected brain. This model could be a useful tool to study host and bacilli factors involved in the pathogenesis of the most severe form of tuberculosis.

Meningitis tuberculosa en niños: una revisión de aspectos clínicos, de laboratorio, epidemiológicos y terapéuticos y de la utilidad de la vacunación con BCG / Tuberculous meningitis in children: a review of clinical, laboratory, epidemiological, and therapeutic aspects and of the usefulness of BCG vaccination

La tuberculosis meníngea (MTB) es la enfermedad tuberculosa extrapulmonar más frecuente en los países del tercer mundo, incluida Colombia, y tiene tasas altas de morbilidad y mortalidad. En este artículo se presenta una revisión de la literatura sobre los siguientes aspectos de la enfermedad: clínicos, epidemiológicos, de laboratorio, tomográficos, terapéuticos y de prevención con la vacuna BCG.

Tuberculous meningitis is the most frequent extrapulmonary form of tuberculosis in underdeveloped countries, among them Colombia. It is associated with high rates of morbidity and mortality. In this article a review is presented of the following aspects of the disease: clinical, epidemiological, therapeutic, prophylactic by means of BCG vaccination, laboratory diagnosis, and tomographic findings.