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

Background: 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-alpha (TNF-alpha) in cerebrospinal fluid (CSF) and its gene expression at mRNA of peripheral blood mononuclear cells (PBMCs). Methods: Fifty-seven patients with TBM were prospectively evaluated. Their clinical findings and severity of meningitis were recorded. The expression of TNF-alpha gene in PBMCs was quantified by real-time polymerase chain reaction and TNF-alpha concentration in CSF by cytokine bead array both in the patients and 14 matched controls. Results: All the patients had history of fever for a median duration of 75 days. The admission temperature ranged between 37.2 degrees C and 40 degrees 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 10 days. The expression of TNF-alpha gene correlated with CSF concentration of TNF-alpha (p = 0.02) and independently predicted duration of defervescence [adjusted hazard ratio 1.02 (95% CI 1.00-1.04; p = 0.01). Conclusion: In the patients with TBM, defervescence takes longer time, and TNF-alpha gene expression predicts the duration of defervescence. Future studies are needed to evaluate the role of TNF-alpha-modifying drugs in TBM.