Worsening CSF parameters after the start of anti-tuberculosis treatment predicts intracerebral tuberculoma development

Abstract

Objectives: We investigated whether early worsening of cerebrospinal fluid (CSF) predicts the later paradoxical tuberculomas and is a potential predictive biomarker.

Methods: Patients of HIV-negative tuberculous meningitis fulfilling the inclusion criteria(n = 98) underwent clinical and CSF evaluation, together with repeated neuroimaging. We compared the baseline clinical data and continuous CSF of patients who did (n = 36) and did not (n = 62) develop paradoxical tuberculomas, and reported the changes associated with symptomatic tuberculomas. A logistic regression analysis was developed to reveal predictors for paradoxical tuberculomas.

Results: The proportion of worsening CSF parameters (WBC count and percent neutrophils) in the paradoxical tuberculomas group (27/36, 75.0%) was significantly higher than the non-paradoxical tuberculomas group (15/62, 24.2%). The logistic regression analysis revealed that worsening CSF parameters was the highest risk predictor for paradoxical tuberculomas. Most worsening CSF parameters (81.0%) occurred within two weeks after treatment (2-24 days, median 7 days), and paradoxical tuberculomas commonly happened two weeks later (12 days to 13 months, median 22 days). The period between worsening CSF parameters and paradoxical tuberculomas ranged from 6 to 383 days (median 21days). There were no significant differences in mortality and prognosis between the two groups.

Conclusions: Early worsening of CSF parameters predicts subsequent development or progression of tuberculomas.

Keywords: Cerebrospinal fluid; HIV negative adults; Paradoxical reactions; Tuberculomas; Tuberculous meningitis.