Lumbar puncture for non-HIV-infected non-transplant patients with cryptococcosis: Should it be mandatory for all?

The indications for lumbar puncture in non-HIV-infected, non-transplant (NHNT) patients with cryptococcosis without meningeal signs need to be more fully defined. This study was designed to determine the optimal predictors of central nervous system (CNS) involvement in adult NHNT patients with cryptococcosis. The 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. We 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. Lumbar puncture is indicated for NHNT patients with cryptococcosis who have neurologic manifestations or a serum CRAG titer of ≥1:64.