Role of cytokines in the assessment of clinical outcome and neuroimaging findings in patients with tuberculous meningitis

Background: Tuberculous meningitis is a life-threatening manifestation resulting from infection by Mycobacterium tuberculosis, especially in the developing countries. The molecular aspects of pathogenesis of tuberculous meningitis remain poorly understood. We evaluated the correlation of cerebrospinal fluid (CSF) and serum cytokine levels with the clinical outcome of 15 HIV-negative patients with tuberculous meningitis. We also assessed the association of CSF and serum cytokines with neuroimaging of brain findings in the patients. Methods: The prospective longitudinal study was conducted at the University Malaya Medical Centre between 2012 and 2014. Neuroimaging of the brain was performed and the findings of leptomeningeal enhancement, hydrocephalus, tuberculoma, infarcts and vasculopathy were recorded. The CSF and serum specimens were analyzed for IL-1ß, IL-8, IL-10, IL-18, IP-10, IFN-γ, MCP-1, TGF-ß, VEGF, TNF- α, IL-18BPa and MMP-9. The clinical outcome was graded at 3 months based on Modified Rankin scale (mRS). Results: On admission and at one month of anti-tuberculosis treatment, the CSF levels of IL-8, IL-1β, IP-10, IFN-γ and VEGF were elevated in all of the patients. Serum IP-10, MCP-1, IL-1β and IL-8 levels were increased on admission and at one month of anti-tuberculosis treatment. There were statistically significant differences between good and poor outcome (mRS at 3 months) for CSF IFN-γ (p=0.033), CSF IL-10 (p=0.033) and serum VEGF (p=0.033) at one month of treatment. None of the patients showed any association between CSF and serum cytokines on admission and at one month of anti-tuberculosis treatment with neuro-radiological findings. Conclusion: The CSF cytokine levels were not related to TBM disease severity on admission, and changes on MRI/CT scans. CSF levels of IFN-γ and IL-10 at one month of anti-tuberculosis treatment were associated with clinical outcome at 3 months. CSF cytokine levels on admission were not associated with the clinical outcome.

Aetiology of viral central nervous system infection, a Malaysian study

Over 100 viruses are known to cause acute viral encephalitis in human. In order to diagnose a viral central nervous system infection, various laboratory diagnosis methods have been used. In this study, we examined 220 cerebrospinal fluid samples that were received at the Diagnostic Virology Laboratory of University Malaya Medical Centre between year 2004 to 2006, by viral isolation, pathogen specific antibody ELISA, polymerase chain reaction (PCR) and Real-Time PCR. Majority of the samples were from patients <10 years old. Out of 220 samples, 3 were positive for viral isolation, 27 for PCR (inclusive for the 3 positive for viral isolation) and 39 for pathogen specific ELISA. The total positive detection rate of this study was 30%. Herpes virus was the most important aetiologic agent, responsible for 58% of infection, followed by paramyxovirus (especially measles virus) in 26% of infection, and 14% by enterovirus. Parvovirus and flavivirus were the other common viruses. Among the herpes viruses, herpes simplex and cytomegalovirus were the most common.