Importance of follow-up cerebrospinal fluid analysis in cryptococcal meningoencephalitis

Abstract

Cryptococcal meningoencephalitis represents a serious infection of the central nervous system, where reliable prognostic factors during the disease course are needed. Twenty-one patients diagnosed with cryptococcal meningoencephalitis in a German university hospital from 1999 to 2013 were analysed retrospectively. CSF parameters were analysed prior to therapy and during antifungal treatment and were compared between patients who survived or deceased. Fifteen patients clinically improved after antifungal therapy, while six patients died. No differences were observed between the outcome groups for the CSF parameters cell count, lactate, total protein, and CSF-serum albumin quotients (QAlb). Follow-up examinations of serum cryptococcal antigen titer and CSF cell count have shown that these parameters cannot be used to monitor the efficacy of antifungal therapy as well. In contrast, the course of QAlb during therapy was indicative for the outcome as a possible prognostic marker. In patients with clinical improvement QAlb values were falling under therapy, while rising QAlb values were found in patients with fatal outcome indicating a continuing dysfunction of the blood-CSF barrier. In conclusion, our results indicate that, among the various CSF parameters, the course of QAlb presents a promising marker that might be used to monitor the efficacy of antifungal therapy.

Figure 1

Examples of abnormal neuroradiological findings in cryptococcal meningoencephalitis. (a) presents the typical pattern of cryptococcal gelatinous pseudocysts located in lentiform and caudate nuclei (T2WI hyperintense signal) while T1WI sequences ((b), arrow head) show a hypointense signal without enhancement in the T1 C+ image ((c), arrow head). Signs of meningitis are shown by leptomeningeal enhancement in the cerebellar Gyri in axial ((d), arrow heads) and coronal (e) T1 C+ scans. (f) presents signs of basal meningitis demonstrated by leptomeningeal enhancement (arrow head). Hydrocephalus is shown in axial FLAIR sequences in (g) and (h). The enlargement of the frontal and dorsal horns of the lateral ventricles with a hyperintense rim of the periventricular white matter indicates a CSF extravasation. A CCT scan performed 5 days later shows increased ballooning of the third ventricle and a progressive enlargement of the lateral ventricles (i).

Figure 2

Illustration of CSF parameters in cryptococcal meningoencephalitis. In (a) values present CSF cell counts while (b)-(c) show values of total CSF protein and CSF-serum albumin quotient (QAlb) after onset of symptoms and during disease course and antifungal therapy. Initial CSF analysis was performed in all patients, while during follow-up CSF was analysed in thirteen patients (eight patients with good outcome and five patients with fatal outcome). Black points mark values of patients with clinical improvement, while red triangles indicate values of patients with the outcome death. On the right side additional graphs present mean values and standard deviation of both groups in the course of antifungal therapy.