We retrospectively analyzed clinical characteristics and laboratory findings in patients with CM in a tertiary hospital in China from 2015 to 2019. Based on the prognosis on discharge, we consider that changes in Qalb value in HIV-negative patients and CSF LDH in HIV-positive patients could be potential prognostic markers.
Aging is a complex and multifaceted process that has a negative impact on the immune system and renders elderly people more susceptible to infectious diseases, including CNS infections [24, 25]. It has been reported that the clinical characteristics of elderly CM patients suggest greater vulnerability to CM [26]. In our cohort, most HIV-negative patients (13/25, 52%) were aged > 60 years (Table 1). Aging may indeed be one of the predisposing factors for CM, but a larger study is needed to confirm this. Race, living habits, and other factors should also be taken into account.
Headache, nausea and/or vomiting, and fever were the most common symptoms. However, it is difficult to distinguish bacterial, fungal and viral meningitis by such symptoms, and delay in diagnosis leads to poor prognosis [26]. Rapid diagnosis of the etiology of meningitis is needed urgently [27]. Disturbance of consciousness and seizures are considered to be poor prognostic factors for CM [28–30]. In the current study, six patients developed disturbance of consciousness before admission and all of them presented with unfavorable outcome. Similarly, 7 of 10 patients with seizures showed poor prognosis. This observation is in line with a previous study [31, 32]. Therefore, CM patients with disturbance of consciousness and/or seizures should receive more aggressive treatment and more granular monitoring.
It has been reported that reactive oxygen species play an essential role in the pathophysiology of meningitis [33]. Changes in serum antioxidant parameters such as albumin, bilirubin and uric acid may have potential as prognostic indicators [31, 32]. In our study, we found varying degrees of significance in the comparison of the above parameters in patients before and after treatment, especially for HIV-positive patients.
HIV-positive patients are usually more likely than HIV-negative patients to have infection with opportunistic pathogens. The dominant mechanism for HIV-induced immunodeficiency is depletion and distortion of CD4+ T cells, and further lymphocyte defects [31, 32]. Therefore, dynamic monitoring of CD4+ T cell counts is critical for HIV-positive patients [34]. In our cohort, there was no significant difference in baseline CD4+ T cell counts at admission between favorable outcome group and unfavorable outcome group. However, the cell counts at discharge were significantly increased compared with before treatment in the favorable outcome group. Our results are consistent with previous reports [35]. Unfortunately, patients with poor prognosis often died of ineffective rescue, and the data after treatment could not be obtained.
The factors related to CSF examination for predicting unfavorable outcome of CM include high CSF opening pressure (> 250 mmH2O), low CSF leukocyte count, high CSF CrAg titer (> 1:1024), decreased CSF glucose concentration, increased CSF protein, decreased CSF chloride and changes in CSF cytokines [28, 36–40]. LDH is ubiquitously distributed in body tissues and it contains five isoenzymes [41]. CSF LDH isoenzymes are comparable in tuberculous and pyogenic meningitis [14]. We found that an increase in CSF LDH may lead to poor outcome in HIV-positive patients (Fig. 3), but there were no similar findings in HIV-negative patients. It has been suggested that cryptococcal meningoencephalitis patients with increased Qalb tend towards a poor outcome [10]. However, that study did not distinguish between HIV-positive and HIV-negative patients. In our study, HIV-negative patients with increased Qalb had poor prognosis (Fig. 4), but the same trend was not found in HIV-positive patients.
There were several limitations to this study. First, this was a retrospective review of medical records in a single hospital. Second, the symptoms and prognosis may differ according to the different serotypes of Cryptococcus [42], but this was not investigated in our study. Further, large prospective multicenter studies are needed to improve the generalizability of our data on CM.