Utility of clinical assessment, imaging, and cryptococcal antigen titer to predict AIDS-related complicated forms of cryptococcal meningitis

From 1990-2009, 82 patients with first episode of cryptococcal meningitis were identified. Of these, 14 (17%) met criteria for complicated forms of cryptococcal meningitis (prolonged altered mental status 6, persistent focal neurologic findings 7, CSF surgical shunt placement 8, and death 5). Patients with complicated cryptococcal meningitis had higher frequency of baseline focal neurological findings, head computed tomography (CT) abnormalities, mean CSF opening pressure, and cryptococcal antigen (CRAG) titers in serum and CSF. ROC area of log2 serum and CSF CRAG titers to predict complicated forms of cryptococcal meningitis were comparable, 0.78 (95%CI: 0.66 to 0.90) vs. 0.78 (95% CI: 0.67 to 0.89), respectively (χ2, p = 0.95). The ROC areas to predict the outcomes were similar for CSF pressure and CSF CRAG titers. In a multiple logistic regression model, the following were significant predictors of the outcome: baseline focal neurologic findings, head CT abnormalities and log2 CSF CRAG titer.During initial clinical evaluation, a focal neurologic exam, abnormal head CT and large cryptococcal burden measured by CRAG titer are associated with the outcome of complicated cryptococcal meningitis following 2 weeks from antifungal therapy initiation.Cryptococcal meningitis remains one of the leading causes of morbidity and mortality in patients with AIDS in resource limited settings [1]. Up to twenty percent of patients with cryptococcal meningitis have minimal central nervous symptoms at clinical presentation and early diagnosis of meningitis is facilitated by use of cerebrospinal fluid (CSF) cryptococcal antigen (CRAG) [2]. Cryptococcal antigen availability and use are variable in developing countries [1]. Over the last twenty years at the University of California, San Diego (UCSD), we occasionally cared for patients with minimal or no symptoms related to the central nervous system, high serum CRAG titer (as high as 1:65,536) and ultimately fatal HIV-associated cryptoc