RESUMO
Resumen La tuberculosis (TBC) cerebral o tuberculoma(s) sin meningitis es una enfermedad poco frecuente y de alta morbimortalidad. Presentamos el caso clínico de un lactante de 11 meses, previamente sano, que consultó por fiebre prolongada y síntomas neurológicos. La RM de encéfalo mostró múltiples imágenes micronodulares e hidrocefalia. El estudio de LCR para bacterias, hongos y micobacterias fue negativo. Se prescribió terapia empírica como una meningoencefalitis subaguda y tratamiento antituberculoso tetraconjugado y corticoesteroides. La confirmación del diagnóstico de TBC cerebral se realizó por biopsia de la lesión, con presencia de inflamación granulomatosa crónica necrosante y bacilos ácido-alcohol resistentes. Se enfatiza la importancia de considerar esta presentación de TBC en niños, y la necesidad de la búsqueda exhaustiva del agente etiológico en diferentes líquidos y tejidos, aun por métodos invasores.
Cerebral tuberculosis TB (tuberculomas) without meningitis is an uncommon disease with a high morbidity and mortality. We report on a case that illustrates the complexity of this clinical presentation. An 11 month old, previously healthy male infant was brought to the clinic due to fever present during the last 1.5 months, associated with loss of neurodevelopmental goals and signs of endocranial hypertension. CT scan of the skull revealed dilatation of the ventricular system with transependimary edema; MRI showed multiple intra- and extra-axial micronodular images and hydrocephalus. Studies of CSF (cyto-chemical analysis, staining, culture for aerobes, fungi, mycobacteria, and molecular tests for TB were negative). Empirical management for subacute meningoencephalitis was prescribed complemented with tetraconjugated treatment for TB and steroids. As there was no microbiological isolation, biopsy of a cerebellar lesion was performed, which revealed chronic necrotizing granulomatous inflammation and acid-alcohol resistant bacilli. The diagnosis of cerebral TB without meningeal involvement was confirmed. The objective of the present report is to emphasize the importance of considering this presentation of TB in children, to remark the need of exhaustive search for the etiologic agent by obtaining samples of the different fluids and tissues even if it implies recurring to invasive methods.
Assuntos
Humanos , Masculino , Lactente , Tuberculose Meníngea/patologia , Tuberculoma Intracraniano/patologia , Tuberculose Meníngea/tratamento farmacológico , Biópsia , Imageamento por Ressonância Magnética , Radiografia Torácica , Tomografia Computadorizada por Raios X , Tuberculoma Intracraniano/tratamento farmacológico , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Diagnóstico Diferencial , Imunocompetência , Meningoencefalite/diagnóstico , Antituberculosos/uso terapêuticoRESUMO
El compromiso del sistema nervioso central por tuberculosis, continúa siendo una causa importante de morbi-mortalidad en los países en vías de desarrollo. Presentamos el caso de una paciente con meningitis y tuberculomas en el sistema nervioso central y discutimos los métodos diagnósticos disponibles en la actualidad para esta patología.
The central nervous system (CNS) involvement due to tuberculosis has been an important cause of morbid-mortality in third world countries. We present a clinical case of a patient with meningitis and CNS tuberculomas, and discuss the diagnostic tests available for this pathology actually.
Assuntos
Sistema Nervoso Central , TuberculoseRESUMO
Central nervous system (CNS) tuberculosis is a serious clinical problem, the treatment of which is sometimes hampered by delayed diagnosis. Clearly, prompt laboratory diagnosis is of vital importance as the spectrum of disease is wideand abnormalities of the cerebrospinal fluid (CSF) are incredibly variable. Since delayed hypersensitivity is the underlying immune response, bacterial load is very low. The conventional bacteriological methods rarely detect Mycobacterium tuberculosis in CSF and are of limited use in diagnosis of tuberculous meningitis (TBM). This double blind study was, therefore, directed to the molecular analysis of CNS tuberculosis by an in-house-developed PCR targeted for amplification of a 240bp nucleotidesequence coding for MPB64 protein specific for Mycobacterium tuberculosis. Based on the clinical criteria, 47 patients with CNS tuberculosis and a control group of 10 patients having non-tubercular lesions of the CNS were included in the study. Analyses were done in three groups; one group consisting of 27 patients of TBM, a second group of 20 patients with intracranial tuberculomas and a third group of 10 patients having non-tubercular lesions of the CNS acted as control. There were no false positive results by PCR and the specificity worked out to be 100 percent. In the three study groups, routine CSF analysis (cells and chemistry), CSF for AFB smear and culture were negative in all cases. PCR was positive for 21/27 patients (77.7 percent sensitivity) of the first group of TBM patients, 6/20 patients (30 percent sensitivity) of the second group with intracranial tuberculomas were positive by PCR and none was PCR-positive (100 percent specificity) in the third group. Thus, PCR was found to be more sensitive than any other conventional method in the diagnosis of clinically suspected tubercular meningitis.
A tuberculose do sistema nervoso central (CNS) é um problema clínico sério, cujo tratamento é dificultado pelo diagnóstico tardio. O diagnóstico laboratorial rápido é de importância vital considerando que o espectro da doença é amplo e as anormalidades do liquor são muito variáveis. Considerando que a hipersensibilidade tardia é a resposta imune fundamental, a carga bacteriana é muito baixa. Os métodos bacteriológicos convencionais raramente detectam Mycobacterium tuberculosis no liquor e são de uso limitado para diagnóstico da meningite tuberculosa (TBM). O presente estudo duplo-cego objetivou a análise molecular da tuberculose do CNS através de um PCR desenvolvido in-house direcionado para a amplificação de uma seqüência de nucleotídios de 240pb que codificam a proteína MPB64 especifica de Mycobacterium tuberculosis. Baseando-se em critérios clínicos, selecionou-se 47 pacientes com tuberculose do CNS e um grupo controle de 10 pacientes com lesões não-tuberculosas no CNS. As análises foram divididas em três grupos: um grupo de 27 pacientes com TBM, um segundo grupo com 20 pacientes com tuberculomas intracraniais e um terceiro grupo de 10 pacientes com lesões não-tuberculosas no CNS (controles). O PCR não forneceu nenhum resultado falso-positivo, com 100 por cento de especificidade. Em todos os três grupos de estudo, os resultados das análises de rotina do liquor por histologia, química e baciloscopia e também cultura foram negativos em todos os casos. No primeiro grupo de pacientes com TBM, PCR foi positivo em 21/27 pacientes (sensibilidade de 77,7 por cento). No segundo grupo de pacientes com tuberculomas intracraniais, 6/20 foram positivos (sensibilidade de 30 por cento). Nenhum dos pacientes do grupo controle foi positivo (100 por cento de especificidade). Dessa forma, o PCR mostrou-se mais sensível que os métodos convencionais no diagnóstico de casos suspeitos de meningite tuberculosa.
Assuntos
Humanos , Técnicas In Vitro , Mycobacterium tuberculosis/isolamento & purificação , Reação em Cadeia da Polimerase , Tuberculoma Intracraniano , Tuberculose do Sistema Nervoso Central , Métodos , Pacientes , Técnicas e Procedimentos DiagnósticosRESUMO
Central nervous system (CNS) tuberculosis is a serious clinical problem, the treatment of which is sometimes hampered by delayed diagnosis. Clearly, prompt laboratory diagnosis is of vital importance as the spectrum of disease is wide and abnormalities of the cerebrospinal fluid (CSF) are incredibly variable. Since delayed hypersensitivity is the underlying immune response, bacterial load is very low. The conventional bacteriological methods rarely detect Mycobacterium tuberculosis in CSF and are of limited use in diagnosis of tuberculous meningitis (TBM). This double blind study was, therefore, directed to the molecular analysis of CNS tuberculosis by an in-house-developed PCR targeted for amplification of a 240bp nucleotide sequence coding for MPB64 protein specific for Mycobacterium tuberculosis. Based on the clinical criteria, 47 patients with CNS tuberculosis and a control group of 10 patients having non-tubercular lesions of the CNS were included in the study. Analyses were done in three groups; one group consisting of 27 patients of TBM, a second group of 20 patients with intracranial tuberculomas and a third group of 10 patients having nontubercular lesions of the CNS acted as control. There were no false positive results by PCR and the specificity worked out to be 100%. In the three study groups, routine CSF analysis (cells and chemistry), CSF for AFB smear and culture were negative in all cases. PCR was positive for 21/27 patients (77.7% sensitivity) of the first group of TBM patients, 6/20 patients (30% sensitivity) of the second group with intracranial tuberculomas were positive by PCR and none was PCR-positive (100% specificity) in the third group. Thus, PCR was found to be more sensitive than any other conventional method in the diagnosis of clinically suspected tubercular meningitis.
RESUMO
Central nervous system (CNS) tuberculosis is a serious clinical problem, the treatment of which is sometimes hampered by delayed diagnosis. Clearly, prompt laboratory diagnosis is of vital importance as the spectrum of disease is wideand abnormalities of the cerebrospinal fluid (CSF) are incredibly variable. Since delayed hypersensitivity is the underlying immune response, bacterial load is very low. The conventional bacteriological methods rarely detect Mycobacterium tuberculosis in CSF and are of limited use in diagnosis of tuberculous meningitis (TBM). This double blind study was, therefore, directed to the molecular analysis of CNS tuberculosis by an in-house-developed PCR targeted for amplification of a 240bp nucleotidesequence coding for MPB64 protein specific for Mycobacterium tuberculosis. Based on the clinical criteria, 47 patients with CNS tuberculosis and a control group of 10 patients having non-tubercular lesions of the CNS were included in the study. Analyses were done in three groups; one group consisting of 27 patients of TBM, a second group of 20 patients with intracranial tuberculomas and a third group of 10 patients having non-tubercular lesions of the CNS acted as control. There were no false positive results by PCR and the specificity worked out to be 100%. In the three study groups, routine CSF analysis (cells and chemistry), CSF for AFB smear and culture were negative in all cases. PCR was positive for 21/27 patients (77.7% sensitivity) of the first group of TBM patients, 6/20 patients (30% sensitivity) of the second group with intracranial tuberculomas were positive by PCR and none was PCR-positive (100% specificity) in the third group. Thus, PCR was found to be more sensitive than any other conventional method in the diagnosis of clinically suspected tubercular meningitis.
A tuberculose do sistema nervoso central (CNS) é um problema clínico sério, cujo tratamento é dificultado pelo diagnóstico tardio. O diagnóstico laboratorial rápido é de importância vital considerando que o espectro da doença é amplo e as anormalidades do liquor são muito variáveis. Considerando que a hipersensibilidade tardia é a resposta imune fundamental, a carga bacteriana é muito baixa. Os métodos bacteriológicos convencionais raramente detectam Mycobacterium tuberculosis no liquor e são de uso limitado para diagnóstico da meningite tuberculosa (TBM). O presente estudo duplo-cego objetivou a análise molecular da tuberculose do CNS através de um PCR desenvolvido in-house direcionado para a amplificação de uma seqüência de nucleotídios de 240pb que codificam a proteína MPB64 especifica de Mycobacterium tuberculosis. Baseando-se em critérios clínicos, selecionou-se 47 pacientes com tuberculose do CNS e um grupo controle de 10 pacientes com lesões não-tuberculosas no CNS. As análises foram divididas em três grupos: um grupo de 27 pacientes com TBM, um segundo grupo com 20 pacientes com tuberculomas intracraniais e um terceiro grupo de 10 pacientes com lesões não-tuberculosas no CNS (controles). O PCR não forneceu nenhum resultado falso-positivo, com 100% de especificidade. Em todos os três grupos de estudo, os resultados das análises de rotina do liquor por histologia, química e baciloscopia e também cultura foram negativos em todos os casos. No primeiro grupo de pacientes com TBM, PCR foi positivo em 21/27 pacientes (sensibilidade de 77,7%). No segundo grupo de pacientes com tuberculomas intracraniais, 6/20 foram positivos (sensibilidade de 30%). Nenhum dos pacientes do grupo controle foi positivo (100% de especificidade). Dessa forma, o PCR mostrou-se mais sensível que os métodos convencionais no diagnóstico de casos suspeitos de meningite tuberculosa.
RESUMO
É relatado o caso clínico de uma criança, previamente hígida, que evoluiu com manifestações neurológicas inespecíficas. O diagnóstico obtido, após investigação intervencionista, foi de neurotuberculose. Instituído tratamento preconizado pela Organização Mundial de Saúde (OMS), com boa resposta clínica. O objetivo é alertar os pediatras para inclusão da neurotuberculose no diagnóstico diferencial de doenças infecciosas e lesões expansivas do sistema nervoso central.
Related a clinical case of a child, previously healthy, who evaluated with unespecific neurological manifestations. The diagnosis obtained, after interventionist investigation, was neurotuberculosis. Instituted treatment extoled by OMS, with good clinical response. The goal is advertise pediatrics to add neurotuberculosis to differential diagnosis of infecctious diseases and expansive lesions of central nervous system.