Abstract
BackgroundThe indications for lumbar puncture in non-HIV-infected, non-transplant (NHNT) patients with cryptococcosis without meningeal signs need to be more fully defined.ObjectivesThis study was designed to determine the optimal predictors of central nervous system (CNS) involvement in adult NHNT patients with cryptococcosis.MethodsThe study population consisted of adult NHNT patients with culture-confirmed cryptococcosis who sought care at a university hospital in Taiwan from 2002 to 2016. We used a case-control method to identify the clinical characteristics and laboratory findings associated with CNS involvement in patients who underwent a diagnostic lumbar puncture. In the sensitivity analysis, we included additional control patients who did not undergo lumbar puncture, but were followed beyond 12 months without the development of CNS involvement in the absence of exposure to any fungicidal agents.ResultsWe entered 270 NHNT adult patients into the study during the 15-year period. CNS involvement was confirmed in 66 (71.0%) of 93 patients who underwent lumbar puncture. A multivariable analysis revealed that presence of neurological manifestations and elevated serum CRAG titers were independently associated with a 23.97-fold (95% confidence interval [CI], 4.37–182.23) and 1.53-fold (per 2-fold increment, 95% CI 1.26–1.92) increased odds ratio for CNS involvement, respectively. Headache and focal neurologic signs were independently associated with CNS involvement. A cut-off serum CRAG titer of ≥1:64 provided the highest diagnostic performance by Youden index (sensitivity 83% and specificity 65%). Similar findings were noted in the sensitivity analysis including 198 (73%) patients.ConclusionLumbar puncture is indicated for NHNT patients with cryptococcosis who have neurologic manifestations or a serum CRAG titer of ≥1:64.
Highlights
Central nervous system (CNS) involvement is the most serious complication of cryptococcosis because of its high mortality and debilitating neurologic sequelae among the survivors [1,2]
A multivariable analysis revealed that presence of neurological manifestations and elevated serum cryptococcal antigen (CRAG) titers were independently associated with a 23.97-fold (95% confidence interval [CI], 4.37–182.23) and 1.53-fold increased odds ratio for CNS involvement, respectively
Lumbar puncture is indicated for NHNT patients with cryptococcosis who have neurologic manifestations or a serum CRAG titer of 1:64
Summary
Central nervous system (CNS) involvement is the most serious complication of cryptococcosis because of its high mortality and debilitating neurologic sequelae among the survivors [1,2]. Non-HIV-infected, non-transplant (NHNT) patients account for a substantial proportion of patients with cryptococcosis [6,7,8,9] Their optimal management is less well defined. NHNT patients with cryptococcosis are reported to have a lower rate of CNS involvement than HIV-infected patients or organ transplant recipients [6,9]. They had a higher mortality rate [6,7,8,9] and severe neurologic morbidities [10,11] when CNS involvement became evident. The indications for lumbar puncture in non-HIV-infected, non-transplant (NHNT) patients with cryptococcosis without meningeal signs need to be more fully defined
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