Clinical study The clinical characteristics of adult cryptococcal meningitis patients who died within one year of treatment with a focus on those with early mortality Wan-Chen Tsai a , Chia-Yi Lien a , Jun-Jun Lee a,b , Chi-Ren Huang a , Nai-Wen Tsai a , Chiung-Chih Chang a , Cheng-Hsien Lu a , Wen-Neng Chang a,⇑ a Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Kaohsiung, Taiwan b Department of Information Management, National Sun Yat-sen University, Kaohsiung, Taiwan article info Article history: Received 2 January 2019 Accepted 9 June 2019 Available online xxxx Keywords: Cryptococcal meningitis Cryptococcemia Altered consciousness Cerebrospinal fluid Lactate level Early mortality abstract Cryptococcal meningitis (CM) is a serious infectious disease of the central nervous system, and associated brain injuries can be found in the very early stage of disease. In this study, 92 adult CM patients (59 men, 33 women; median age 54.66 years, range 20–86 years) were enrolled, and their clinical, laboratory, neuroimaging features and therapeutic outcomes were analyzed. Two main clinical comparative analyses of the clinical characteristics and laboratory and neuroimaging features were made in this study. The first compared clinical differences between the survivors and non-survivors of all enrolled patients, and the second compared differences between the following three groups: Group I, the patients who died within 14 days of initiating treatment; Group II, the patients who died within 15 days to 1 year of initiating treatment, and Group III, the patients who survived for more than 1 year after initiating treatment. Prognostic factors including initial altered consciousness, increased cerebrospinal fluid (CSF) lactate level and the presence of cryptococcemia were significantly different between the different groups. The patients with early mortality had a higher CSF lactate level and higher rate of cryptococcemia. The pres- ence of cryptococcemia was an important prognostic factor, and the patients with cryptococcemia had a higher incidence of positive CSF India ink stain. Further large-scale studies are needed to delineate the clinical and laboratory features of CM patients with early mortality. Ó 2019 Elsevier Ltd. All rights reserved. 1. Introduction Despite advances in diagnostic and therapeutic strategies, cryp- tococcal meningitis (CM) remains a serious infectious disease of the central nervous system (CNS) [1,2]. In clinical practice, the anti- fungal treatment of CM involves sequential, longitudinal therapeu- tic phases including the induction phase, consolidation phase and secondary prophylaxis if needed [3,4]. Previous studies have reported CM patients with a fulminant clinical course who died in the induction phase of treatment, however no previous study has focused on the clinical characteristics of this early mortality patient group. Therefore, in this study, we analyzed the clinical characteristics and laboratory findings of adult CM patients who died within 1 year of initiating treatment, with a particular focus on those who died in the induction phase of therapy in order to delineate the clinical characteristics of this specific group of CM patients with early mortality. 2. Patients and methods We retrospectively reviewed the clinical manifestations, labora- tory data and initial neuroimaging features of adult patients (18 years of age) newly diagnosed with CM and admitted to Kaohsiung Chang Gung Memorial Hospital during a 15-year study period (2002–2016). During this study period, a total of 99 adult CM patients were identified. Seven patients were lost to follow- up after being discharged from hospital, and they were excluded from this study. The remaining 92 CM patients were enrolled for analysis. This study was approved by the Ethics Committee of Kaohsiung Chang Gung Memorial Hospital (IRB No:1608300002). In this study, CM was defined as either (1) isolation of C. neoformans in one or more cerebrospinal fluid (CSF) cultures, a positive CSF cryptococcal antigen (Ag) titer, or positive CSF India ink staining and clinical features of meningitis; or (2) isolation of https://doi.org/10.1016/j.jocn.2019.06.015 0967-5868/Ó 2019 Elsevier Ltd. All rights reserved. ⇑ Corresponding author at: Department of Neurology, Chang Gung Memorial Hospital-Kaohsiung, 123, Ta Pei Road, Niao Sung Hsiang, Kaohsiung, Taiwan. E-mail address: cwenneng@ms19.hinet.net (W.-N. Chang). Journal of Clinical Neuroscience xxx (xxxx) xxx Contents lists available at ScienceDirect Journal of Clinical Neuroscience journal homepage: www.elsevier.com/locate/jocn Please cite this article as: W.-C. Tsai, C. Y. Lien, J. J. Lee et al., The clinical characteristics of adult cryptococcal meningitis patients who died within one year of treatment with a focus on those with early mortality, Journal of Clinical Neuroscience, https://doi.org/10.1016/j.jocn.2019.06.015