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Correlation of CSF Proinflammatory Cytokines with MRI in Tuberculous Meningitis

Posted Jan 31, 2010 Updated Apr 7, 2023
By Abhishek Yadav MSc , Chaynika Chaudhary MBBS , Anuradha H. Keshavan MD , Atul Agarwal DM , Sanjay Verma MSc , Kashi N. Prasad MD , Ram Kishore S. Rathore PhD , Richa Trivedi PhD , Rakesh K. Gupta MD
9 min read

Rationale and Objectives

To demonstrate the correlation of proinflammatory cytokines (PCs), intercellular adhesion molecule (sICAM-1), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β) in CSF of tuberculous meningitis (TBM) patients with magnetic resonance imaging (MRI) including diffusion tensor imaging (DTI) and also to look for the changes in imaging parameters after antitubercular treatment (ATT) in these patients.

Materials and Methods

Forty patients with TBM (median age, 27.7 years) and 30 age-/sex-matched controls were included in this study. PCs were quantified from the CSF of TBM patients at the time of hospital admission (baseline). MRI including DTI was performed at the time of baseline study and 6 months after ATT.

Results

Significant positive correlation of PCs with fractional anisotropy (FA) values and post-contrast signal intensity (PCSI) collected from cerebral cortical regions was observed in TBM patients. A significant positive correlation of FA values with PCSI was also observed at both time points in patient groups. At baseline study significantly high FA values were observed in patients compared to controls. Significantly decreased FA values and PCSI were observed in the patients after 6 months of ATT compared to the baseline study.

Conclusions

Results of this study suggest that the DTI-derived anisotropy have the potential to delineate meningeal inflammation and it may be used in assessment of therapeutic response in TBM patients as an additional method to conventional imaging.

Tuberculous meningitis (TBM) is the most devastating form of tuberculosis and is associated with high morbidity and mortality worldwide . Its prevalence is increasing globally and is becoming a major problem in the Western world because of the increasing number of immunocompromised and to multidrug-resistant patients with tuberculosis TBM is fatal in 25% of adults and causes neurological sequelae in 25% of survivors even after the administration of modern chemotherapy .

In TBM, bacilli seed to brain parenchyma or meninges to form Rich foci. These foci rupture with release of bacilli in to subarachnoid space and stimulates release of proinflammatory cytokines (PCs) (eg, tumor necrosis factor-α [TNF-α], interleukin-1β [IL-1β]) and also increases the concentration of white blood cells in cerebrospinal fluid (CSF) . TNF-α has been shown to be associated with the development of TBM pathology in vivo, including tissue necrosis and cachexia . It is produced in response to the bacterial pathogen and mediates the upregulation of adhesion molecules such as selectins, intercellular adhesion molecules (ICAMs), and vascular cell adhesion molecules . IL-1β and TNF-α, are also responsible for the development of granuloma in TBM patients . In experimental bacterial meningitis, TNF-α has been shown to be responsible for the blood-brain barrier permeability as well as leukocytosis . Tsenova et al observed that TNF-α promote the progression of TBM in murine model .

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Materials and methods

Subjects

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CSF Culture

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Enzyme-linked Immunosorbent Assay

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Imaging Protocol

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PCSI and DTI Data Processing and Quantification

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Figure 1, Magnetic resonance images from a 24-year-old male (control). The elliptical regions of interest (ROIs) were placed in the cerebral cortical regions (a) localized on the diffusion-weighted images (DWI) (b = 1000) to ensure the absence of cerebral spinal fluid contamination. Color-coded fractional anisotropy (FA) map (b) modulated by the principal eigenvector showing normal distribution of signal intensities in brain parenchyma.

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Figure 2, Magnetic resonance images at baseline study (a-f) from 20-year-old male with tuberculous meningitis (TBM). Postcontrast (PC) T1-weighted images (a, d) show intense meningeal enhancement in cortical and basal regions. Segmented region of enhanced meninges (b, e) as seen on PC T1-weighted images show 796.37 ± 83.02 and 748.82 ± 72.75 PC signal intensity (PCSI) in cortical and basal region, respectively. Color-coded fractional anisotropy (FA) maps (c, f) modulated by the principal eigenvector show increased FA values in the cerebral cortical (0.15 ± 0.03) and basal region (0.15 ± 0.02) (arrows) corresponding to intense meningeal enhancement seen on PC T1 (a, d) compared to control (0.10 ± 0.02) ( Figure 1 ). Follow-up magnetic resonance images (g-l) after 6 months of antitubercular treatment (ATT) from the same patient. After 6 months of ATT, patient developed a ring-enhanced tuberculoma in the right thalamic region (g) and basal region (j) . PC T1-weighted images (g, j) as well as segmented (h, k) images show less enhanced meningeal membrane in both cortical (PCSI = 610.99 ± 143.92) and basal (PCSI = 592.40 ± 23.51) regions on follow-up than baseline study. Color-coded FA maps (i, l) modulated by the principal eigenvector show decreased FA values (0.13 ± 0.02) after ATT compared to baseline.

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Statistical Analysis

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Results

Laboratory Examinations

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Qualitative Image Analysis

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Quantitative Analysis

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Correlation among PCs, DTI Metrics, and PCSI at the Time of Baseline Study

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Figure 3, Plots (a, b) showing relationship among proinflammatory cytokines (PCs) (tumor necrosis factor-α [TNF-α], soluble intercellular cell adhesion molecules-1 [sICAM-1], and interleukin-1β [IL-1β]), fractional anisotropy (FA) values and postcontrast signal intensity (PCSI) in TBM patients. (c, d) Relationship between FA and PCSI on baseline as well as follow-up study, respectively.

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Comparison of DTI Metrics in TBM Patients with Healthy Controls

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Comparison of DTI Metrics in TBM Patients between Baseline and Follow-up Study

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Comparison of PCSI in TBM Patients between Baseline and Follow-up Study

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Discussion

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Academic Radiology, Volume 17, Issue 2
Journals General Radiology
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