Inflammatory biomarkers as predictors of paradoxical reaction in tubercular meningitis: a prospective observational...

Tubercular meningitis (TBM) is associated with high morbidity and mortality due to intense inflammatory responses causing basal exudates, vasculitic infarcts, hydrocephalus and cranial nerve palsies. Paradoxical reaction (PR) occurs in nearly 30% of patients and contributes to clinical deterioration during treatment. Dysregulated inflammatory mediators in serum and cerebrospinal fluid (CSF) have been implicated in PR and adverse outcomes in TBM.

This study evaluated baseline serum and CSF inflammatory biomarkers for predicting PR and vasculitic infarcts in newly diagnosed TBM patients.

In this prospective observational study, 151 treatment-naïve TBM patients fulfilling Marais consensus criteria were enrolled. Baseline clinical, radiological, serum and CSF inflammatory markers were assessed and repeated during PR/stroke. Serum markers included high-sensitivity C reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), lactate dehydrogenase (LDH), ferritin, albumin, D-dimer, neutrophil-lymphocyte ratio (NLR) and systemic immune-inflammation index. CSF analysis included adenosine deaminase, NLR, protein, glucose and leucocyte count.

Among 151 patients (mean age 32.7±14.5 years), 43 (28.4%) developed PR, most commonly within 1-2 months of antitubercular therapy initiation. Altered sensorium (58.1%) and progression of hydrocephalus (60.5%) were common manifestations. Higher baseline ESR, hsCRP, LDH, ferritin, D-dimer and lower serum albumin were significantly associated with PR. Serum ferritin showed the best predictive accuracy (area under the curve 0.910; cut-off ≥451 µg/L; sensitivity 88.4%, specificity 88.9%). On multivariable analysis, serum ferritin (OR 1.004; p=0.001) and ESR (OR 1.020; p=0.033) remained independent predictors.

Serum inflammatory markers, particularly ferritin and ESR, may serve as useful predictors of PR in TBM. These findings support an immune-mediated mechanism underlying paradoxical worsening and may help identify high-risk patients who could benefit from early anti-inflammatory or immune-modulatory therapy.