Role of Oxidative Stress in Tuberculous Meningitis: a Clinico-Radiological Correlation Jayantee Kalita 1 & Usha K. Misra 1 & Ashish K. Dubey 1 Received: 4 February 2019 /Accepted: 18 March 2019 # Springer Science+Business Media, LLC, part of Springer Nature 2019 Abstract Central nervous system infection may be associated with oxidative stress and may influence clinical severity and outcome. We report oxidative stress markers in the patients with tuberculous meningitis (TBM) and correlate these with clinico-radiological severity and outcome. Fifty-six patients with TBM diagnosed on the basis of clinical, cerebrospinal fluid (CSF), and magnetic resonance (MRI) were included. Plasma glutathione (GSH), total antioxidant capacity (TAC), and malondialdehyde (MDA) were measured in the patients and 55 matched healthy controls. Hospital death was noted. Disabilities at 3 and 6 months were categorized using the modified Rankin Scale (mRS) as poor (mRS > 2) or good (mRS ≤ 2). The patients had lower levels of GSH (1.49 ± 0.49 vs 2.57 ± 0.39 mg/dL, p ˂ 0.001) and TAC (0.25 ± 0.17 vs 2.20 ± 0.31 mmol Trolox Eq/L, p ˂ 0.001), and higher level of MDA (6.61 ± 1.72 vs 3.09 ± 0.38 nmol/mL, p < 0.001) compared to controls. Total antioxidant capacity correlated with cranial nerve palsy and CSF pleocytosis. Patients with tuberculoma had lower GSH compared to those without. Six patients died in the hospital, and they had lower GSH (p < 0.01) and TAC (p = 0.02) levels compared to those who survived. Thirty-one and 36 patients had a good outcome at 3 and 6 months respectively. The patients with good outcome had higher GSH level. Keywords Tuberculous meningitis . Oxidative stress . Glutathione . Total antioxidant capacity . Malondialdehyde . MRI . Tuberculoma Introduction Tuberculosis is a global health problem, and there is a resur- gence of tuberculosis even in the countries where it has be- come rare (WHO 2016). The annual incidence of tuberculosis varies from 9 cases/100,000 populations in the USA to 110– 165 cases/100,000 population in the developing countries (Raviglione et al. 1995). About 10% of the patients with extra pulmonary tuberculosis have central nervous system (CNS) involvement. Tuberculous meningitis (TBM) is the most severe form of tuberculosis resulting in high mortality (20–30%) and neurological sequel in 25–50% (Misra et al. 2011; Kalita et al. 2007, 2009; Thwaites and Hie 2005; Marais et al. 2010). Computerized tomographic (CT) scan and magnetic resonance imaging in TBM reveal exudates, stroke, hydrocephalous, tuberculoma, or tubercular abscess in isolation or in various com- binations (Misra et al. 2011; Gupta et al. 1994). In experimental studies on bacterial meningitis, there have been growing evi- dences of oxidative stress-mediated brain injury and neurological complications. Leucocytes and macrophages migrate to the site of bacterial infection to destroy the microorganism. The activated macrophages including central nervous system (CNS) immune cells consume more oxygen thereby liberating reactive oxygen species (ROS), which in turn produce toxic superoxide anions, H 2 O 2 , and hydroxyl radicals. In a normal situation, ROS is neu- tralized by cellular enzymatic (superoxide dismutase and catalase) and non-enzymatic antioxidants (glutathione, uric acid, etc.). Inability to neutralize excess production of ROS leads to an im- balance in oxidative and antioxidant activity resulting in lipid peroxidation and DNA breakdown (Sies 1997; Levonen et al. 2014). Central nervous system infection and stroke are regarded Highlights • The patients with tuberculous meningitis have increased oxidative stress. • The lower level of antioxidant is associated with death and poor outcome. • Role of augmenting antioxidant or reducing stress may be explored in the outcome of tuberculous meningitis. * Usha K. Misra drukmisra@rediffmail.com; ukmisra@sgpgi.ac.in 1 Department of Neurology, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow 226014, India Journal of Molecular Neuroscience https://doi.org/10.1007/s12031-019-01304-0