Tuberculous meningitis is the most common presentation of intracranial tuberculosis , and usually refers to infection of the leptomeninges. The remainder of this article pertains to leptomeningeal tuberculosis, which involves the arachnoid mater and pia mater. In low prevalence areas, it is more frequently encountered in adolescents and adults. Most common clinical manifestations are fever, headache, vomiting and neck stiffness. Seizures, focal neurological deficits, stupor and coma may be seen in late stages.
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Metrics details. Tuberculous meningitis is the most devastating presentation of disease with Mycobacterium tuberculosis.
We sought to evaluate treatment outcomes for adult patients with this disease. We pooled appropriate data to estimate treatment outcomes at the end of treatment and follow-up. Among the articles identified, 22 met our inclusion criteria, with patients.
In a pooled analysis, the risk of death was The risk of neurological sequelae among survivors was Patients diagnosed in stage III or human immunodeficiency virus HIV positive were significantly more likely to die The frequency of cerebrospinal fluid CSF acid-fast-bacilli smear positivity was We found that the headache, fever, vomiting, and abnormal chest radiograph were the most common symptoms and diagnostic findings among tuberculous meningitis patients.
Despite anti-tuberculosis treatment, adult tuberculous meningitis has very poor outcomes. Peer Review reports. Tuberculosis, caused by Mycobacterium tuberculosis MTB , remains one of the leading causes of infection-related mortality worldwide [ 1 ]. In , an estimated 10 million incident cases of tuberculosis were recorded globally with approximately 1. Tuberculous meningitis is especially common in children and those infected with human immunodeficiency virus HIV , in whom outcomes are poor [ 2 , 5 ].
Early diagnosis, prompt anti-tuberculosis treatment and corticosteroids are the main determinants of outcome in tuberculous meningitis [ 2 ]. However, early diagnosis of tuberculous meningitis remains a great challenge because symptoms such as fever, headache, vomiting and so on, are not specific. Since identification of acid-fast bacilli in the cerebrospinal fluid CSF and culture of MTB lack sensitivity, the diagnosis of tuberculous meningitis is often based on clinical suspicion combined with empirical decision making [ 3 ].
The following clinical stages are defined: stage I: fully conscious patient with no focal neurological deficits; stage II: there is altered sensorium but not to the degree of coma and minor focal neurological deficits such as a single cranial nerve palsy; stage III: marked alteration of level of consciousness, coma.
This type of classification is useful to predict prognosis. Without treatment, tuberculous meningitis leads to death. An effective treatment regimen recommended by the World Health Organization WHO consists of isoniazid, rifampicin, and pyrazinamide, usually with a fourth drug such as ethambutol or streptomycin, as first-line anti-tuberculosis drugs in patients with tuberculous meningitis [ 9 , 10 ].
In addition to effective anti-tuberculosis treatment, adjuvant corticosteroid treatment is also recommended for tuberculous meningitis patients [ 2 , 4 , 9 , 10 ]. There were many studies described the treatment outcome for tuberculous meningitis, but the results varied between studies due to inconsistent diagnostic criteria, treatment methods, study populations and settings.
A previous systematic review of research showed that the prognosis of tuberculous meningitis in children are very poor, Especially for patients in stage III [ 5 ]. However, outcomes for adult patients have not been systematically reviewed. Therefore, this systematic review and meta-analysis were performed to evaluate the prognosis of adult tuberculous meningitis. Our primary objective was to establish risks of death in adult tuberculous meningitis patients during treatment.
Additionally, we reported the pooled frequencies of symptoms and diagnostic findings at presentation. For duplicative or overlapping publications, the study with the largest sample size was included. Studies obtained from the literature search were checked by title and abstract. Relevant studies were examined in full text. Two authors MG W and YX Z independently screened all potentially relevant studies and tried to reach a consensus on all items.
Any disagreements were assessed by a third author XM L. The diagnosis of tuberculous meningitis was based on clinical, CSF, radiological criteria and evidence of tuberculosis elsewhere [ 11 ]. At least 2 points should either come from CSF or cerebral imaging criteria [ 11 ]. The following data were extracted from each study: treatment outcomes, characteristics of studies and patients, and frequencies of symptoms and diagnostic results. Outcome indicators included death, neurological sequelae, and lost-to-follow-up treatment abandonment or loss to follow-up.
Survival is defined as being alive at the time of completion of treatment. Neurological sequelae are defined as any motor, sensory, cognitive, or hypothalamic impairment that emerged during the disease and continuous the treatment period. The quality of individual studies was assessed with only high quality studies included for analysis. Microsoft Excel version The random effects model was used to generate summary effect.
Logit transformation was used for all meta-analyses. First, we pooled all studies to estimate the risk of death and the proportion of survivors in adult patients with tuberculous meningitis during treatment. To further explore the relationship between disease severity and treatment outcome, studies that stratified outcomes by BMRC or the modified BMRC disease stage were used to calculate the risk of death at different disease stages during treatment [ 6 , 8 ].
Secondly, we also pooled the demographic characteristics of all patients, including the frequencies of symptoms and diagnostic results. A flow chart outlining our literature search is shown in Fig. We identified 16, publications from our initial database search. After removal of repetitive studies, articles were screened by titles and abstracts. Of these, articles were identified for full text review and 90 articles were not assessed for eligibility.
Two hundred and thirty-six studies were removed prior to analysis, as shown in Fig. The basic characteristics of the included studies are shown in Table 1. Of the 22 eligible studies, 11 were retrospective chart reviews, 9 were prospective cohorts, and two were randomized controlled trial.
The study periods ranged from to The study populations of these studies came from nine countries. Seventeen studies were conducted in countries currently on the WHO list of countries with high TB burden [ 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 27 , 28 , 29 , 31 ].
The majority of patients were male In studies with available data, The 22 cohorts included data from patients. All tuberculous meningitis patients received anti-tuberculosis treatment. Among adult tuberculous meningitis patients, risk of death was Among survivors, risk of neurological sequelae was By summarizing the results of 17 studies that stratified treatment outcomes according to disease stages, we found that the risk of death was significantly higher among patients diagnosed in stage III Considerable heterogeneity was observed for all outcomes.
Subgroup analyses were conducted to investigate the sources of heterogeneity, including study type, BMRC disease stage, HIV infection, treatment duration, and the use of streptomycin Table 2. Unfortunately, we can not fully explain the heterogeneity of the research.
The most common features of patients were fever, headache, vomiting, weight-loss, abnormal chest radiograph and basilar enhancement Table 3. Among 17 studies stratified patients by disease severity, Nearly The frequency of CSF acid-fast-bacilli smear positivity was All these pooled proportions showed significant between study heterogeneity. This systematic review and meta-analysis estimated the treatment outcomes among adult tuberculous meningitis patients.
The findings suggested that the treatment outcomes for adult patients with tuberculous meningitis are poor. To the best of our knowledge, this is the first meta-analysis to access the treatment outcome of tuberculous meningitis among adults. More importantly, our subgroup analyses indicated that mortality increased with the severity of the disease. The more serious the disease was, the worse the treatment outcome was.
Furthermore, tuberculous meningitis patients who were HIV positive had higher mortality. According to the WHO, 9. Our study found that approximately It has been reported that tuberculosis patents co-infected with HIV were more likely to have poor treatment outcome and death [ 34 , 35 ]. Consisted with those studies, our results showed half of HIV-positive tuberculous meningitis patients died during the treatment, which was significantly higher than HIV negative patients Early diagnosis of tuberculous meningitis is a great challenge for early treatment as there are limitations in the current widely used methods, such as the low sensitivity of the acid-fast bacilli smear and the long turn-around time of mycobacterial culture [ 36 ].
In this study, the definite diagnostic rate was Recently, rapid, sensitive and highly specific molecular detection methods have been favored [ 1 , 37 , 38 ]. CSF molecular diagnostic methods nucleic acid amplification tests have previously been included in diagnostic criteria for tuberculous meningitis [ 37 , 38 ].
While we found fever, headache, vomiting and weight-loss were the most common symptoms among tuberculous meningitis patients, these nonspecific clinical presentations are and thus may contribute to delayed diagnosis [ 2 ].
Hence, clinicians should be vigilant against the disease, and suspected patients should be treated with anti-tuberculosis drug based on rich clinical experience without waiting for confirmatory testing. Effective anti-tuberculosis therapy is crucial for the treatment outcome of tuberculous meningitis.
We excluded 56 of full-text articles that do not specify treatment regimens, and 9 for lack of follow-up time or incomplete anti-tuberculosis treatment. Our results showed that the mortality of tuberculous meningitis was nearly in patients treated with streptomycin Which means neither the use streptomycin or not has no significant effect on treatment outcome.
While the studies utilized the same regimens for tuberculous meningitis, the treatment durations were varied between studies [ 4 , 9 , 39 ]. Duo to the high mortality and sequelae of tuberculous meningitis, we believe that the course of treatment should be individualized. Substantial heterogeneity was found between studies. Although we detected subgroup analysis based on the characteristics of the included studies, we still can not fully explain the source of heterogeneity.
Although we failed to determine the source of heterogeneity, the following factors may related to heterogeneity. First, the different study designs of included studies, which might have led to the heterogeneity of the results. However, the similar result detected in prospective cohort study subgroups, reinforced our conclusion.
Meningitis - tuberculous
Metrics details. Tuberculous meningitis is the most devastating presentation of disease with Mycobacterium tuberculosis. We sought to evaluate treatment outcomes for adult patients with this disease. We pooled appropriate data to estimate treatment outcomes at the end of treatment and follow-up. Among the articles identified, 22 met our inclusion criteria, with patients. In a pooled analysis, the risk of death was
Treatment outcomes of tuberculous meningitis in adults: a systematic review and meta-analysis
Purpose of review: As the most severe form of tuberculosis TB , TB meningitis disproportionately affects developing countries and results in significant morbidity and mortality. In this report, we review recent updates in the epidemiology, diagnosis, and management of TB meningitis. Early diagnosis remains challenging, especially since conventional diagnostic tests have sub-optimal sensitivity and specificity. Recently, nucleic acid amplification testing emerged as the preferred diagnostic modality due to its rapid turnaround time and high specificity. Several recent studies have assessed the optimal treatment for TB meningitis. While the benefit of treatment intensification, by increasing rifampin dosing or adding a fluoroquinolone, is unclear, a growing body of evidence suggests that steroids confer a survival advantage, particularly in patients with mild disease.