Incidence, risk factors and treatment of central nervous system immune reconstitution inflammatory syndrome in non-HIV patients with tuberculous meningitis: a multicentre observational study

Abstract

Background: Immune reconstitution inflammatory syndrome (IRIS) affecting the central nervous system (CNS) is associated with poor outcomes.

Aims: To report on risk factors for CNS-IRIS following tuberculous meningitis (TBM) in HIV-negative patients.

Methods: In this retrospective multicentre study, all HIV-negative adult patients admitted between 2003 and 2021 with microbiologically proven TBM were included. The primary outcome measure was IRIS onset over follow-up. Characteristics of patients who developed IRIS were described. Factors associated with IRIS were identified using a multivariable logistic regression procedure.

Results: Fifty-six patients (33.0 (27.0-44.3) years, 39 (69.6%) men) with microbiologically proven TBM were studied. All patients received antituberculosis treatment and 48 (n = 48/56; 85.7%) steroids at TBM diagnosis. During a median follow-up of 18.0 (12.0-27.3) months, IRIS occurred in 28 (n = 28/56, 50.0%) patients, at a median time of 2.0 (1.0-3.0) months after antituberculosis treatment was started. IRIS involved the CNS in all but one case. Imaging revealed new (n = 23/28, 82.1%) and/or worsening (n = 21/28; 75.0%) of previously recognised lesions. Multivariable analysis showed that meningeal enhancement on brain magnetic resonance imaging (MRI) (odds ratio (OR): 15.3; 95% confidence interval (CI): (1.19-1193.5)) at TBM diagnosis and high blood albumin level (OR: 1.21; 95% CI: (1.02-1.60)) were associated with the occurrence of CNS-IRIS during follow-up.

Conclusion: CNS-IRIS following TBM in non-HIV patients appears frequent and severe. Meningeal enhancement on brain MRI at tuberculosis diagnosis is a risk factor for CNS-IRIS.

Keywords: central nervous system; immune reconstitution inflammatory syndrome; risk factors; tuberculous meningitis.