Pooled analysis of the Xpert MTB/RIF assay for diagnosing tuberculous meningitis.

BACKGROUND: Tuberculous meningitis (TBM) is one of the most serious types of extrapulmonary tuberculosis. However, low sensitivity of culture of cerebrospinal fluid (CSF) increases the difficulty in clinical diagnosis, leading to diagnostic delay, and misdiagnosis. Xpert MTB/RIF assay is a rapid and simple method to detect tuberculosis. However, the efficacy of this technique in diagnosing TBM remains unclear. Therefore, a meta-analysis was conducted to evaluate the diagnostic efficacy of Xpert MTB/RIF for TBM, which may enhance the development of early diagnosis of TBM. METHODS: Relevant studies in the PubMed, Embase, and Web of Science databases were retrieved using the keywords 'Xpert MTB/RIF', 'tuberculous meningitis (TBM)'. The pooled sensitivity, pooled specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, summary receiver operator characteristic curve, and area under the curve (AUC) of Xpert MTB/RIF were determined and analyzed. RESULTS: A total of 162 studies were enrolled and only 14 met the criteria for meta-analysis. The overall pooled sensitivity of Xpert MTB/RIF was 63% [95% confidence interval (CI), 59-66%], while the overall pooled specificity was 98.1% (95% CI, 97.5-98.5%). The pooled values of positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio were 20.91% (12.71-52.82%), 0.40% (0.32-0.50%), and 71.49% (32.64-156.56%), respectively. The AUC was 0.76. CONCLUSIONS: Xpert MTB/RIF exhibited high specificity in diagnosing TBM in CSF samples, but its sensitivity was relatively low. It is necessary to combine other high-sensitive detection methods for the early diagnosis of TBM. Moreover, the centrifugation of CSF samples was found to be beneficial in improving the sensitivity.

[A case of tuberculous meningitis with pleural effusion as a manifestation of a paradoxical reaction during anti-tuberculosis therapy].

We present a case of tuberculous meningitis (TBM), wherein pleural effusion developed as a manifestation of paradoxical reaction during anti-tuberculosis therapy. An 87-year-old diabetic man was referred to our clinic for fever and impaired consciousness. He did not obey vocal commands. No ocular motor deficit, facial palsy, or limb weakness was observed. He had hyponatremia due to inappropriate antidiuresis. Examination of the cerebrospinal fluid revealed lymphocytosis and high adenosine deaminase (ADA) activity, suggestive of TBM. He was treated with isoniazid, rifampicin, and pyrazinamide, after which his symptoms quickly resolved. Lymphocyte count, ADA activity, and protein concentration in the cerebrospinal fluid decreased. However, approximately 30 days after the initiation of therapy, he developed mild hypoxemia. A chest CT scan revealed pleural effusion. The pleural fluid was exudate with elevated ADA activity, which was consistent with tuberculous pleural effusion. Shortly after the use of a herbal medicine, Goreisan extract, hyponatremia and hypoproteinemia improved, and the pleural effusion was reduced. Approximately one-third of patients with TBM are reported to develop a paradoxical reaction, such as tuberculoma, hydrocephalus, and optochiasmatic and spinal arachnoiditis. The present case suggests that extra-central nervous system manifestations, including pleural effusion, should be considered when treating TBM.

Correlation of clinical, laboratory and drug susceptibility profiles in 176 patients with culture positive TBM in a tertiary neurocare centre.

Drug resistance has increased the difficulties in control of tuberculosis infection. The present study evaluated the clinical and laboratory features among tuberculous meningitis (TBM) patients and the drug susceptibility of Mycobacterium tuberculosis (M.tb) isolated from CSF. Out of 698 CSF samples, 176 (25.21%) were M.tb culture positive. Among the clinical signs and symptoms, fever, headache and altered sensorium were found to be statistically significant (P<0.05). ELISA was a better predictor of disease and found to be statistically significant (P<0.001) in culture-proven TBM cases. Totally, 57 (32.4%) isolates were resistant to one or more drugs that include 5 (2.8%) multidrug-resistant isolates. In conclusion, the search for antibody in CSF and also CSF chloride can represent as an adjunct in the diagnosis of TBM. Screening of drug susceptibility is a very important factor and would help in better management of the disease.

Successful Treatment of a Child With Extensively Drug-Resistant Tuberculous Meningitis.

Unlike in pulmonary multidrug-resistant (MDR) tuberculosis, the clinical outcome of MDR tuberculous meningitis (TBM) in children, including extensively drug-resistant tuberculosis, is poor and management is challenging. We report the successful treatment of a case of extensively drug-resistant TBM in a 4-year-old girl, and we discuss implications for tuberculosis diagnosis and chemotherapy.

Diagnosis and therapy of tuberculous meningitis in children.

Children are among the subjects most frequently affected by tuberculous meningitis (TBM) due to their relative inability to contain primary Mycobacterium tuberculosis infection in the lung. TBM is a devastating disease with about 30% mortality among the most severe cases; moreover, 50% of survivors have neurological sequelae despite an apparently adequate administration of antibiotics. Early diagnosis and prompt treatment are crucial for reducing the risk of a poor outcome. However, especially in children, the best and most rapid way to confirm the diagnosis is controversial; the optimal choice, dose, and treatment duration of anti-tuberculosis drugs are not precisely defined, and the actual importance of adjunctive therapies with steroids and neurosurgery has not been adequately demonstrated. This review is an effort to discuss present knowledge of the diagnosis and treatment of pediatric TBM in order to offer the best solution to address this dramatic disease. In conclusion, we stress that new studies in children are urgently needed because data in the early years of life are more debatable than those collected in adults. In the meantime, when treating a child with suspected TBM, the most aggressive attitude to diagnosis and therapy is necessary, because TBM is a devastating disease.

[Treatment of tuberculous meningitis]. / Traitement des tuberculoses cérébro-méningées.

INTRODUCTION: Tuberculous meningitis and brain tuberculomas are currently rare in the western world but remain serious. Improved outcome requires early recognition and treatment of these conditions. STATE OF ART: Treatment is usually begun before diagnostic confirmation. Therapeutic principles are now better defined thanks to recent recommendations and studies. Antituberculous therapy begins with two months of a combination of four drugs: isoniazid, rifampicin, ethambutol and pyrazinamid. Then follows a longer phase of bitherapy with isoniazid and rifampicin, lasting at least four months but usually extended to seven or ten months as a precaution. Patients at risk of toxic neuropathy should receive pyridoxine supplementation. Corticosteroids must be systematically added during the first eight weeks of treatment, beginning with high dose before progressive tapering. Hyponatremia is common, often induced by emesis and cerebral salt wasting syndrome. Therefore saline supply rather than water restriction is required. Non-obstructive hydrocephaly can usually be managed with diuretic therapy including acetazolamid, sometimes complemented by serial lumbar punctures. Neurosurgical interventions are rarely needed. Monitoring of treatment tolerance and efficacy is mainly clinical. Central nervous system imaging and cerebro-spinal fluid analysis are only required to explain clinical deterioration. CONCLUSION: With adequate and prompt anti-tuberculous, anti-inflammatory and supportive treatment, the prognosis of central nervous system tuberculosis can be greatly improved.

Meningitis tuberculosa en adultos: análisis de 53 casos / Tuberculous meningitis in adults: review of 53 cases

La meningitis tuberculosa (MTBC) es la forma más grave de tuberculosis extrapulmonar. El amplio espectro del cuadro clínico y su poca especificidad dificultan su diagnóstico precoz, relacionándose directamente con mayor letalidad. El objetivo de este estudio es analizar las características clínicas de los pacientes con diagnóstico de MTBC en el Hospital de Enfermedades Infecciosas Dr. Lucio Córdova, de Santiago, Chile, entre 1995 y 2002. Se estudiaron 53 casos de MTBC en adultos, con una edad mediana de 39 años. Al ingreso 66 por ciento de los pacientes presentaba algún grado de compromiso de conciencia, pero sólo 30 por ciento la tríada sintomática clásica. El LCR mostró aumento de proteínas, glucosa baja y linfocitosis, en la mayoría de los casos. Treinta por ciento de los pacientes presentó co-infección con VIH; la letalidad en este grupo de pacientes fue mayor, 31 vs 17 por ciento del total de la muestra. La MTBC continúa siendo una enfermedad vigente. El diagnóstico de certeza precoz de esta patología no es posible con los métodos actuales, por lo que la sospecha clínica es importante.

[Acute onset of tuberculous meningoencephalitis presenting with symmetric linear lesions in the bilateral thalamus: a case report].

A 18-year-old woman was admitted to our hospital because of high fever and headache. Nuchal stiffness was present, and a CSF examination showed lymphocyte-domonant pleocytosis and a decreased level of glucose. Although antibiotics, aciclovir and an antimycotic drug were administered, disturbance of consciousness, involuntary movements, and pyramidal tract signs appeared. Soon after the medications were changed to antituberculous medicines, the meningoencephalitis started to subside, and was finally cured. Judging from the clinical findings, the CSF findings, the effectiveness of antituberculous medicines, an elevated ADA level in CSF, and positive conversion in tuberculin tests, the final diagnosis was made as tuberculous meningoencephalitis. At the severest stage of the disease, a brain MRI showed symmetric, linear lesions without the effect of Gd-enhancement in the bilateral thalamus, which thereafter disappeared along with the healing of the illness. From all these things, we conclude that thalamic and other parenchymal lesions should be kept in mind in case of acute tuberculous meningoencephalitis.

Dementia associated with dorsal midbrain lesion.

Although the dorsal midbrain has been implicated in cognitive processes in animals, its role in humans is unclear. We report the neuropsychological and postmortem neuropathological findings of a 52-yr-old university professor who developed a profound dementia in association with a focal dorsal midbrain lesion. The patient's disorder appeared to result from a tuberculous granuloma based on the clinical course and autopsy results. Neuropsychologically, he exhibited a generalized impairment across most of the cognitive domains assessed. His deficits were not explained by impaired arousal, specific sensory or motor defects, depression, or hydrocephalus. Although there are inherent limitations to a single-case investigation, our observations are consistent with animal studies that have demonstrated that focal dorsal midbrain lesions may result in cognitive impairment. We propose that the dorsal midbrain is involved in cognitive processing via modulation of thalamocortical networks.