Paradoxical reactions in pediatric HIV-negative CNS tuberculosis: A longitudinal cohort study

Paradoxical reactions (PR) in pediatric HIV-negative CNS tuberculosis remain underexplored. This study prospectively analyzes incidence and pattern of PR and its impact on functional outcome.

Children (6 months-14 years) with newly diagnosed CNS Tuberculosis using the Lancet Consensus Scoring System, were enrolled. All participants received standard anti-tubercular therapy (ATT). Clinical evaluation, CSF analysis and neuroimaging were performed at baseline, during clinical worsening, or at 8 weeks. PR patterns defined as worsening or new tuberculosis lesions or symptoms following initial improvement after ≥10 days of ATT, were documented. Functional outcomes were assessed at 6-months using the Pediatric Cerebral Performance Category (PCPC) scale.

Of the 57 participants enrolled [04 with rifampicin resistance were excluded; 24/53 had deterioration within initial 12-weeks of which 17 children qualified for PR (32%; median onset-3.5 weeks; range: 2-7 weeks). Two children developed late-onset PR beyond 12 weeks. [Total PR = 19 (Early-17; Late-2)] Common clinical features included focal neurological deficits (47%) and fever (42%). Prominent radiological patterns were infarction (47%), new or enlarging tuberculomas (37%) and spinal arachnoiditis (37%). Thirteen of 19 cases required additional anti-inflammatory treatment. BMRC Stage 2 and 3 independently predicted PR. PR was associated with unfavourable outcome on PCPC scale (adjusted OR = 34.3; 95% CI: 3.42-343.71; p = 0.001).

PR occurs in approximately one-third of pediatric HIV-negative CNS tuberculosis cases, typically early in treatment. Early recognition is essential to distinguish PR from disease progression or drug resistance and to avoid inappropriate treatment modifications.