Predictors of fever response in tuberculous meningitis: A clinical, MRI and biomarker study.

Abstract

Central nervous system (CNS) has a different immune surveillance system; therefore, fever at admission and timeline of fever response after antitubercular treatment (ATT) may follow a different course in CNS infection. We report the predictors of fever response in tuberculous meningitis (TBM) including the effect of tumour necrosis factor-α (TNF-α) in cerebrospinal fluid (CSF) and its gene expression at mRNA of peripheral blood mononuclear cells (PBMCs). Fifty-seven patients with TBM were prospectively evaluated. Their clinical findings and severity of meningitis were recorded. The expression of TNF-α gene in PBMCs was quantified by real-time polymerase chain reaction and TNF-α concentration in CSF by cytokine bead array both in the patients and 14 matched controls. All the patients had history of fever for a median duration of 75days. The admission temperature ranged between 37.2°C and 40°C and correlated with CSF cell counts (p<0.05). Cranial MRI was abnormal in 54 (94.7%) and revealed exudates in 33(57.9%), hydrocephalus in 27(47.4%), infarction in 27(47.4%) and tuberculoma in 33(57.9%) patients. Fever subsided after a median duration of 18 (2 60)days of treatment. Twelve (21.8%) patients only became afebrile within 10days. The expression of TNF-α gene correlated with CSF concentration of TNF-α (p=0.02) and independently predicted duration of defervescence [adjusted hazard ratio 1.02 (95% CI 1.00-1.04; p=0.01). In the patients with TBM, defervescence takes longer time, and TNF-α gene expression predicts the duration of defervescence. Future studies are needed to evaluate the role of TNF-α-modifying drugs in TBM.