Tuberculous meningitis is the most severe form of central nervous system tuberculosis. Mycobacterium tuberculosis reaches the meninges through the bloodstream and sets up a chronic inflammatory process concentrated at the base of the brain, where the basal cisterns become filled with thick, gelatinous exudate. This basal meningitis can compress cranial nerves, obstruct cerebrospinal fluid flow and damage blood vessels, producing hydrocephalus, infarction and a wide range of neurological deficits. Even with modern anti-tuberculous drugs and corticosteroids, mortality and disability remain high, particularly when diagnosis is delayed.

Paradoxical reactions add a cruel twist to this already difficult disease. In a paradoxical reaction, a patient initially improves on anti-tuberculous therapy, then deteriorates neurologically despite the drugs continuing to kill the bacteria. The prevailing explanation is immunological: as anti-tuberculous drugs reduce the bacterial load, they also strip away antigens that had been dampening the immune response, allowing a rebound of cell-mediated immunity directed at residual mycobacterial antigens. Tumor necrosis factor-alpha and other inflammatory mediators surge, granulomatous inflammation flares, and lesions that had been shrinking can enlarge or appear at new sites. Paradoxical worsening is well documented in HIV-negative patients and in HIV-positive patients after starting antiretroviral therapy, a related phenomenon known as immune reconstitution inflammatory syndrome.

The Sri Lankan team, led by Shanindra de Alwis of the University of Sri Jayewardenepura with colleagues from the University of Colombo and the Institute of Neurology at the National Hospital of Sri Lanka, focused on one of the most destructive forms this rebound can take. Optochiasmatic arachnoiditis involves the optic nerves and the chiasmatic cisterns, the fluid-filled spaces surrounding the optic chiasm where fibers from both eyes cross. Inflammation and fibrosis in this region entrap the optic pathways, causing progressive, often irreversible loss of vision. Because the optic chiasm sits directly above the suprasellar cistern and within reach of the basal inflammatory exudate of tuberculous meningitis, it is uniquely vulnerable when paradoxical inflammation flares at the base of the brain.

All three patients in the series followed the same ominous trajectory. Each initially improved after starting anti-tuberculous therapy, consistent with the drugs doing their job. Then, during the course of treatment, they developed new neurological deterioration and radiological changes consistent with a paradoxical reaction. Neuroimaging revealed suprasellar tuberculomas, granulomatous masses in the region above the pituitary fossa, together with basal cisternal involvement affecting the optic pathways in every case. The pattern of optochiasmatic arachnoiditis was thus visible on magnetic resonance imaging as inflammatory disease encasing the structures that carry visual signals from the eyes to the brain.

Managing these patients proved extraordinarily difficult. Treatment required prolonged high-dose corticosteroid therapy to suppress the runaway inflammatory response, an approach that carries its own substantial risks when maintained for months. In selected cases, the team added adjunctive immunomodulatory therapy, including thalidomide, a drug with potent anti-tumor necrosis factor-alpha activity that has been used experimentally in severe central nervous system tuberculosis and in refractory paradoxical reactions. Thalidomide’s mechanism is relevant here: by inhibiting tumor necrosis factor-alpha, it aims to blunt the very cytokine driving the granulomatous flare, offering a targeted way to calm inflammation that corticosteroids alone could not control.

The outcomes were grim. Despite intensive immunosuppressive therapy, two patients died from complications related to prolonged immunosuppression. The surviving patient experienced persistent visual deficits, a lasting reminder that even when life is saved, the optic pathways damaged by optochiasmatic arachnoiditis may never fully recover. The authors emphasize that optochiasmatic arachnoiditis represents a rare but catastrophic paradoxical complication of tuberculous meningitis in HIV-negative patients, a population in whom paradoxical reactions are less commonly anticipated than in patients with HIV who begin antiretroviral therapy.

The series carries important lessons for clinicians worldwide. First, deterioration during anti-tuberculous therapy is not always treatment failure. Distinguishing paradoxical reactions from drug resistance, inadequate dosing or alternative diagnoses is essential, because the management strategies differ fundamentally: paradoxical worsening calls for intensified immunosuppression, not for changing anti-tuberculous drugs. Second, new visual symptoms in a patient being treated for tuberculous meningitis should prompt urgent neuroimaging of the suprasellar and chiasmatic regions, because early recognition of optochiasmatic arachnoiditis may allow intervention before irreversible fibrosis entombs the optic nerves. Third, the fatal complications of prolonged immunosuppression in two patients highlight the double-edged nature of the available therapies, which must suppress a destructive immune flare without leaving the patient defenseless against infection and other steroid-related harms.

The immunopathology underlying paradoxical reactions remains incompletely understood, and the authors argue that improved understanding is essential to guide targeted adjunctive therapies and improve outcomes. The interplay between mycobacterial antigen load, cell-mediated immunity, tumor necrosis factor-alpha and other cytokines determines whether residual disease smolders quietly or erupts into granulomatous inflammation around the optic chiasm. Better biomarkers to predict which patients will flare, and immunomodulatory agents that can be deployed with precision rather than through prolonged blunt immunosuppression, are the goals the field must pursue. For now, this Sri Lankan case series stands as a stark warning: the very success of anti-tuberculous therapy can ignite an inflammatory backlash capable of stealing a patient’s sight, and in the most severe cases, their life.

Published as an open access case report in BMC Infectious Diseases, the study adds to the growing recognition that central nervous system tuberculosis is not merely an infectious disease but an immunological battleground. As tuberculosis continues to affect millions globally, and as drug-resistant strains prolong treatment courses and expand the window for paradoxical events, awareness of optochiasmatic arachnoiditis among neurologists, infectious disease specialists and ophthalmologists could make the difference between timely intervention and permanent blindness. The Sri Lankan experience shows that vigilance during the treatment of tuberculous meningitis must extend beyond bacterial cure to the immune consequences of that cure itself.

Subject of Research: Health & Medicine

Article Title: Optochiasmatic arachnoiditis as a paradoxical reaction in tuberculous meningitis: a case series from Sri Lanka

Article References: de Alwis, S., Chandrasiri, D., Ruwanpathirana, P., Fernando, A., & Senanayake, B. (2026). Optochiasmatic arachnoiditis as a paradoxical reaction in tuberculous meningitis: a case series from Sri Lanka. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14471-4

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14471-4

Keywords: tuberculous meningitis, optochiasmatic arachnoiditis, paradoxical reaction, central nervous system tuberculosis, thalidomide, corticosteroids, Sri Lanka, BMC Infectious Diseases, Optochiasmatic, arachnoiditis, paradoxical, reaction