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A Clinico-Immunological Perspective of Paradoxical Reaction in HIV-ve Tuberculous Meningitis with Therapeutic Possibilities
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A Clinico-Immunological Perspective of Paradoxical Reaction in HIV-ve Tuberculous Meningitis with Therapeutic Possibilities
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Journal Article
A Clinico-Immunological Perspective of Paradoxical Reaction in HIV-ve Tuberculous Meningitis with Therapeutic Possibilities
2025
Overview
Tuberculous meningitis (TBM) is a critical form of tuberculosis with high morbidity and mortality. Paradoxical reactions (PR) are frequently observed in neurotuberculosis, with diverse manifestations. A selective immune dys/upregulation leads to cytokine surge. The exact immune pathogenesis is not known. This review explores the established literature-based knowledge in PR in HIV-ve TBM to visualize the gray zone in neurotuberculosis and possible immune therapeutic adventures. We undertook this systematic review as per the preferred reporting items for systematic reviews and meta-analyses guidelines and searched PubMed, Scopus, Embase, and Google Scholar database till July 25, 2024, to identify eligible studies focusing on PR in TBM/neurotuberculosis. Quality assessment followed the protocol of Murad MH et al. Data were synthesized narratively and statistically analyzed using Microsoft Excel. The search yielded 112 records describing 617 patients. PR is an immune dys/upregulated state in tuberculosis observed with a median age of 34 years (7-74 years), incidence of 12.7-64.7%, and 9.09-27.8% mortality. The spectrum involved clinical PR (tuberculomas, hydrocephalus, infarcts, arachnoiditis), imaging PR, cerebrospinal fluid PR, or in combinations. Treatment in the form of medical [corticosteroid, thalidomide, intrathecal hyaluronidase, biological (anti-tumor necrosis factor-alpha/TNF-α agents)], surgery (ventriculoperitoneal shunting) has shown good clinical response. Immunological and genetic studies in PR/neurotuberculosis are sparse. Immunological agents like corticosteroid, thalidomide, biologicals like anti-TNF-α have proven benefit in treating PR/neurotuberculosis. Research into the neuroimmunological and genetic aspects of PR is lacking and needs further exploration via predictive models and randomized therapy-based trials.
