RESUMO
Tuberculosis (TB) of the central nervous system (CNS) is a lethal and incapacitating disease. Several studies have been performed to understand the mechanism of bacterial arrival to CNS, however, it remains unclear. Although the interaction of the host, the pathogen, and the environment trigger the course of the disease, in TB the characteristics of these factors seem to be more relevant in the genesis of the clinical features of each patient. We previously tested three mycobacterial clinical isolates with distinctive genotypes obtained from the cerebrospinal fluid of patients with meningeal TB and showed that these strains disseminated extensively to the brain after intratracheal inoculation and pulmonary infection in BALB/c mice. In this present study, BALB/c mice were infected through the intranasal route. One of these strains reaches the olfactory bulb at the early stage of the infection and infects the brain before the lungs, but the histological study of the nasal mucosa did not show any alteration. This observation suggests that some mycobacteria strains can arrive directly at the brain, apparently toward the olfactory nerve after infecting the nasal mucosa, and guides us to study in more detail during mycobacteria infection the nasal mucosa, the associated connective tissue, and nervous structures of the cribriform plate, which connect the nasal cavity with the olfactory bulb.
RESUMO
BACKGROUND: Tuberculous meningitis (TBM) is the most frequent, severe, and disabling form of central nervous system (CNS) tuberculosis (TB). TBM paradoxical manifestations are characterized by clinical or paraclinical worsening after 1 month of effective anti-TB treatment in patients who initially responded to treatment despite the use of adjunctive corticosteroids. METHODS: Retrospective descriptive study of consecutive HIV-negative adult patients (≥ 18 years) with definitive TBM who developed a paradoxical manifestation following anti-TB in a tertiary-care hospital in Mexico from 2009 to 2019; we also conducted a literature review of published cases/series of paradoxical manifestations in HIV-negative patients from 1980 to 2020. RESULTS: We detected 84 cases of definitive TBM; 55 (68.7%) HIV-negative patients and 29 (36.3%) HIV-infected patients. Among HIV-negative patients, four (7.3%), three female and one male (19-49 years old), developed a paradoxical manifestation within 4-14 weeks following treatment initiation despite receiving adequate corticosteroid doses; Mycobacterium bovis was isolated from the cerebrospinal fluid of three cases and Mycobacterium tuberculosis in one more. Two patients developed vasculopathy-related cerebral infarctions, one severe basilar meningitis, and hydrocephalus, one more a tuberculoma. Two were treated with intravenous cyclophosphamide, and two with steroids. One of the patients treated with steroids died; patients who received cyclophosphamide had a good clinical response. CONCLUSIONS: This case series illustrates the diverse clinical/radiologic paradoxical manifestations of TBM in HIV-negative patients. Cyclophosphamide may be safe and effective in treating TBM-associated paradoxical manifestations. Specific diagnostic and care protocols for these patients are needed.
Assuntos
Infecções por HIV , Mycobacterium tuberculosis , Tuberculose Meníngea , Adulto , Antituberculosos/uso terapêutico , Feminino , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tuberculose Meníngea/líquido cefalorraquidiano , Tuberculose Meníngea/complicações , Tuberculose Meníngea/tratamento farmacológico , Adulto JovemRESUMO
Animal models are and will remain valuable tools in medical research because their use enables a deeper understanding of disease development, thus generating important knowledge for developing disease control strategies. Central nervous system tuberculosis (CNS TB) is the most devastating disease in humans. Moreover, as the variability of signs and symptoms delay a timely diagnosis, patients usually arrive at the hospital suffering from late stage disease. Therefore, it is impossible to obtain fresh human tissue for research before an autopsy. Because of these reasons, studies on human CNS TB are limited to case series, pharmacological response reports, and post mortem histopathological studies. Here, we review the contribution of the different animal models to understand the immunopathology of the disease and the host-parasitic relationship, as well as in the development of new strategies of vaccination and to test new drugs for the treatment of CNS TB.
Assuntos
Modelos Animais de Doenças , Tuberculose do Sistema Nervoso Central/imunologia , Animais , Antituberculosos/uso terapêutico , Vacinas contra a Tuberculose , Tuberculose do Sistema Nervoso Central/etiologia , Tuberculose do Sistema Nervoso Central/terapiaRESUMO
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.