Paradoxical reaction in tuberculous meningitis: Presentation, predictors and impact on prognosis

Abstract

Background: Awareness about paradoxical reactions in tuberculous meningitis is crucial as aparadoxical reaction may lead to certain wrong conclusions (for example, anerroneous diagnosis, and a possibility of treatment failure, mycobacterial drug-resistance, drug toxicity, or presence of a malignancy). The present study was planned to evaluate the incidence andpredictive factors of paradoxical reactionsin light of clinical, cerebrospinal fluid, and neuroimaging characteristics. Methods: In this prospective cohort study, consecutive patients fulfilling the International Consensus criteria of tuberculous meningitis were included. Patients were subjected to clinical evaluation, cerebrospinal fluid evaluation, and neuroimaging. Patients were treated with anti-tuberculosis drugs along with corticosteroids. Patients were regularly followed up at 3 monthly intervals. At each follow up patients were evaluated clinically and repeat cerebrospinal fluid analysiswas performed along with repeat neuroimaging. Disability assessment was done using Barthel index. Results: We enrolled 141 patients of tuberculous meningitis. Approximately one-third of patients (44/141; 31.2%) developed aparadoxical reaction. Twenty-seven patients developed hydrocephalus, 26 developed tuberculomas, 12 developed optochiasmatic arachnoiditis and 4 patients had spinal arachnoiditis. In 41 patients (out of 44) cerebrospinal fluid paradoxically worsened (increase in cells and/or protein); 2 demonstrated a decrease in cells with polymorph predominance while in one it was normal. In 3 patients, paradoxical cerebrospinal fluid changes were not associated with neuroimaging changes. On multivariate analysis, predictors of paradoxical reaction were female gender (p = 0.013), HIV positivity (p = 0.01) and a shorter duration of illness (p = 0.049). Development of paradoxical reactions did not predict the disability status of the patients. Conclusions: Paradoxical reaction occurs in approximately one-third of patients with tuberculous meningitis. Female gender, concomitant HIV infection, and a shorter duration of illness were significant predictors. Paradoxical reactions did not adversely affect the outcome.