European Journal of Cardiovascular Medicine

Tuberculous meningitis (TBM) is the most severe and life-threatening form of neuro-tuberculosis, associated with substantial morbidity and mortality despite standardized therapy. It accounts for a disproportionately high burden of neurological sequelae among affected survivors, particularly in countries with high tuberculosis prevalence. The disease results from hematogenous dissemination of Mycobacterium tuberculosis to the central nervous system, followed by rupture of subependymal or meningeal Rich foci into the subarachnoid space, producing dense basal exudates, vasculitis, cranial-nerve entrapment, and obstructive hydrocephalus (1,2). These mechanisms underlie the broad clinical spectrum of TBM, ranging from mild meningitic symptoms to profound coma and extensive focal neurological deficits.

Magnetic resonance imaging (MRI) plays a pivotal role in the diagnosis and monitoring of TBM, offering superior soft-tissue contrast, multiplanar imaging capabilities, and heightened sensitivity for detecting meningeal inflammation, infarcts, tuberculomas, and ventricular abnormalities (3,4). Classical MRI features—basal meningeal enhancement, communicating hydrocephalus, infarction in perforator territories, and parenchymal granulomas—are well documented in neuroradiological literature (3,4,11). MRI techniques continue to evolve, with advances in structural imaging and quantitative sequences enhancing lesion characterization and diagnostic accuracy (5,7). The incorporation of gadolinium-enhanced three-dimensional MP-RAGE imaging has further improved delineation of meningeal and parenchymal pathology (9,10).

While MRI provides detailed depiction of pathological changes, the relationship between specific radiological findings and clinical severity at presentation remains insufficiently explored. Several studies have shown high rates of imaging abnormalities in TBM, but the strength of association with clinical staging, neurological deficits, or consciousness levels has varied. For instance, Yadav et al. reported correlations between CSF proinflammatory cytokines and MRI abnormalities, highlighting the interplay between inflammation and radiological severity (6). However, data linking MRI features directly to clinical severity scales—such as the British Medical Research Council (BMRC) staging or Glasgow Coma Scale—are limited, especially in resource-constrained settings where imaging-based prognostication could greatly influence early management strategies.

India, as a high-burden region for tuberculosis, faces considerable challenges in early recognition of severe TBM due to delayed presentation, limited neurosurgical facilities, and restricted access to advanced diagnostics. Identifying MRI markers that correlate with clinical severity can assist in risk stratification, guide treatment intensification, and potentially predict poor outcomes. Furthermore, improving image quality, minimizing motion artefacts, and optimizing structural sequences are essential for accurate assessment in critically ill patients (8).Given these considerations, there is a compelling need to evaluate how MRI abnormalities reflect clinical severity in TBM systematically.

This was a hospital-based observational cross-sectional study conducted in the Department of Radiodiagnosis, in collaboration with the Department of medicine and radiology , at a tertiary care teaching hospital. A total of 100 consecutive patients clinically diagnosed with tuberculous meningitis (TBM) were included in the study. The sample size was predetermined based on feasibility, institutional case load, and the requirement to achieve adequate statistical power for correlation analysis.

Eligibility Criteria

Inclusion Criteria

1. Patients aged ≥ 18 years diagnosed with tuberculous meningitis based on clinical features, CSF analysis, and supportive imaging findings.
2. Patients who underwent MRI brain with contrast at presentation.
3. Those classified clinically into severity stages (I, II, III) based on the British Medical Research Council (BMRC) staging system or equivalent neurological severity scales.

Exclusion Criteria

1. Patients with contraindications to MRI (e.g., pacemakers, ferromagnetic implants).
2. Patients with coexisting CNS infections (bacterial, viral, fungal) or malignancy.
3. Previously treated TBM patients or those already on anti-tubercular therapy for more than 7 days.
4. Incomplete imaging studies or poor-quality MRI due to motion artefacts.

Clinical Assessment

All enrolled patients underwent a detailed clinical evaluation at admission. Clinical severity of TBM was graded using the BMRC staging system:

• Stage I: Alert, no focal neurological deficits
• Stage II: Altered consciousness or mild focal deficits
• Stage III: Severe altered consciousness, dense neurological deficits, or coma

Additional clinical parameters recorded included duration of symptoms, Glasgow Coma Scale (GCS), presence of seizures, cranial nerve involvement, and focal neurological deficits.

Laboratory Investigations

All patients underwent standard laboratory evaluation including:

• CSF analysis (cell count, protein, glucose, ADA levels)
• CSF smear or GeneXpert/CBNAAT when available
• Blood investigations: CBC, ESR, CRP, blood glucose, renal and liver function tests

These were documented but not used as primary correlates in this study.

MRI Protocol

MRI of the brain was performed on a 1.5 Tesla or 3 Tesla scanner using a standardized institutional protocol.

Sequences Acquired

• Axial and sagittal T1-weighted imaging
• Axial T2-weighted imaging
• FLAIR sequences
• Diffusion-weighted imaging (DWI) with ADC mapping
• T2/FLAIR for ventricles and cisterns
• Post-contrast T1-weighted sequences in axial, coronal, and sagittal planes
• MRV/MRA (when clinically indicated)

MRI Features Evaluated

1. Basal meningeal enhancement
2. Hydrocephalus (communicating or non-communicating)
3. Infarcts (location, number, vascular territory)
4. Tuberculomas (size, number, location, enhancement pattern)
5. Cerebritis or edema
6. Cranial nerve enhancement
7. Vascular complications (vasculitis, arterial narrowing, thrombosis)
8. Leptomeningeal or pachymeningeal involvement

Each MRI parameter was assessed independently by two experienced radiologists blinded to clinical severity. Disagreements were resolved by consensus.

Data Collection and Grouping

Patients were categorized into three groups based on clinical severity:

• Group I – Mild (Stage I)
• Group II – Moderate (Stage II)
• Group III – Severe (Stage III)

MRI findings were recorded in a structured proforma. Clinical and radiological data were subsequently matched for correlation.

Statistical Analysis

Data analysis was performed using SPSS (version 25).

• Categorical variables were expressed as frequencies and percentages.
• Continuous variables were represented as mean ± standard deviation or median (IQR) as appropriate.
• Correlation between MRI findings and clinical severity was assessed using:
• Chi-square test / Fisher’s exact test for categorical variables
• ANOVA or Kruskal–Wallis test for continuous variables
• Spearman correlation coefficient for ordinal relationships
• A p-value < 0.05 was considered statistically significant

The demographic profile of the study participants is summarized in Table 1. The mean age of the study population was 42.7 ± 15.3 years, with a median of 40 years, indicating that TB meningitis predominantly affected middle-aged adults. A progressive increase in age was observed across the BMRC severity stages, with patients in Stage III demonstrating the highest mean age (50.6 ± 16.3 years). This age difference was statistically significant (ANOVA, p = 0.003), suggesting that increasing age may be associated with greater disease severity. The sex distribution showed a male predominance (58%), yet the comparison of sex across severity groups did not reveal a significant association (p = 0.29), implying that sex does not influence the clinical severity of TB meningitis in this study.

Table 1. Demographic Distribution of the Study Population (n = 100)

Detailed MRI characteristics across the three clinical severity categories are presented in Table 2. Basal meningeal enhancement was the most frequent abnormality and demonstrated a clear gradient across severity levels—from 56.2% in Stage I to 96.3% in Stage III (p = 0.002). This pattern underscores the role of intense basal exudation in the pathophysiology of advanced TBM. Hydrocephalus exhibited a similarly strong association with severity, affecting 85.2% of patients in Stage III compared to only 31.2% in Stage I (p < 0.001). Infarctions were also significantly more common in severe stages, particularly Stage III (74.1%), reflecting the impact of tuberculous vasculitis on neurological deterioration.

Table 2. MRI Findings Across Clinical Severity Groups

Tuberculomas were present across all stages, with their highest prevalence in Stage III (63%). However, the association with severity approached but did not reach statistical significance (p = 0.059), indicating that the presence of tuberculomas alone may not reliably predict severe disease. Cranial nerve enhancement and parenchymal edema showed strong and progressive associations with severity (p = 0.001 and p < 0.001, respectively), reinforcing the view that these findings reflect advanced inflammatory and parenchymal involvement.

The composite MRI burden score, illustrated in Table 3, showed a marked stepwise increase from Stage I (mean score 1.4 ± 0.9) to Stage III (mean score 3.8 ± 1.3). The strong positive correlation between MRI burden score and clinical severity (Spearman ρ = 0.62, p < 0.001) indicates that disease severity increases proportionally with the number of MRI abnormalities identified. This relationship highlights the diagnostic and prognostic value of cumulative MRI findings in TB meningitis.

Table 3. Summary of MRI Burden Score and Clinical Severity

To further explore these associations, Table 4 presents the individual correlation coefficients between each MRI parameter and clinical severity. Infarctions (ρ = 0.58) and parenchymal edema (ρ = 0.61) showed the strongest correlations, followed by hydrocephalus (ρ = 0.52) and cranial nerve enhancement (ρ = 0.46). Basal meningeal enhancement demonstrated a moderate correlation (ρ = 0.43). Tuberculomas exhibited only a weak correlation (ρ = 0.21), consistent with earlier observations.

Table 4. Correlation Between MRI Abnormalities and Clinical Severity (Spearman’s Rank Correlation)

Collectively, the results across Tables 1–4 demonstrate that several MRI features—particularly hydrocephalus, infarction, parenchymal edema, and cranial nerve involvement—serve as robust radiological markers of clinical severity in TB meningitis. The strong correlation between MRI burden and disease stage suggests that MRI may be a valuable adjunct for early risk stratification and prognostication.

In this prospective study of 100 patients with tuberculous meningitis (TBM), we found that older age was significantly associated with higher clinical severity (mean age: Stage I 36.4 ± 12.1 years; Stage II 44.7 ± 14.8 years; Stage III 50.6 ± 16.3 years; p = 0.003). This suggests that advancing age may predispose to more severe disease presentation, a finding that aligns with prior observations that older age is a risk factor for poorer outcome in TBM.

Our data show that basal meningeal enhancement was present in 56.2% of Stage I, 78.0% of Stage II, and 96.3% of Stage III patients (p = 0.002). This progressive increase is consistent with published literature. For instance, a comprehensive review reports leptomeningeal enhancement in up to 90% of TBM cases.(12) The meta-analysis data suggest that basal cisternal enhancement is the most sensitive MRI feature of TBM (reported range ~38–89%). The high rate of enhancement in our Stage III group underscores a strong association between extensive meningeal exudation on MRI and greater clinical severity.(13)

In our study hydrocephalus was seen in 31.2% of Stage I, 51.2% of Stage II, and 85.2% of Stage III (p < 0.001). This strong correlation supports the notion of hydrocephalus as a key radiological marker of severity. In published studies, hydrocephalus has been reported in around 60–75% of TBM adult cases. (14) One review of children found rates up to 80% in paediatric TBM. Our higher figure in Stage III suggests that among patients with advanced TBM, hydrocephalus is highly prevalent and may act as a poor-prognosis indicator. We found cerebral infarcts in 18.7% of Stage I, 41.4% of Stage II and 74.1% of Stage III (p < 0.001). This again confirms that infarction burden increases with severity. Prior data show infarcts in about 15–28% of cases.(15) The discrepancy between our higher Stage III prevalence and earlier literature may reflect our stricter stratification by clinical severity and perhaps improved imaging sensitivity (MRI rather than CT). The presence of infarcts likely reflects advanced vasculitic involvement of cerebral vessels by tubercular exudates. (16)

In our study tuberculomas occurred in 34.3% of Stage I, 46.3% of Stage II, and 63.0% of Stage III; however, the association with severity was only borderline significant (p = 0.059). Literature reports tuberculomas in about 27% of TBM patients. The weaker association with severity suggests that while tuberculomas are part of the radiological spectrum of TBM, their presence may not be as tightly linked to clinical stage compared to meningeal enhancement, hydrocephalus or infarcts.(15)We observed cranial nerve enhancement in 12.5% of Stage I, 26.8% of Stage II, and 55.5% of Stage III (p = 0.001); and parenchymal edema in 9.3% of Stage I, 31.7% of Stage II and 70.4% of Stage III (p < 0.001). These strong associations reflect advancing brain parenchymal involvement with worsening disease, a pattern that is less frequently quantified in older studies but consistent with pathophysiology of TBM (extension of exudates into brain tissue, secondary inflammation, vasogenic edema).The composite MRI burden score in our study increased from mean 1.4 ± 0.9 in Stage I to 3.8 ± 1.3 in Stage III, and the Spearman correlation with severity was ρ = 0.62 (p < 0.001). This moderate-to-strong correlation supports the concept that cumulative imaging abnormalities reflect disease severity. Few previous studies have quantified this kind of cumulative score, but the finding is congruent with the concept that more imaging abnormalities translate to worse clinical status.

Our study strengthens and extends prior work in several ways: (1) by using a sizeable sample (n = 100) with clear stratification of clinical severity; (2) showing graded increases in MRI abnormalities across severity stages; (3) quantifying a burden score and correlation; and (4) confirming older age as a factor in severity. While older reviews have described typical MRI findings (meningeal enhancement, hydrocephalus, infarcts). Our focus on correlation with severity adds a prognostic dimension.Clinically, the strong associations observed suggest that MRI findings (especially hydrocephalus, infarcts, parenchymal edema) may help clinicians stratify patients at high risk for poor outcomes and may therefore influence decisions regarding early aggressive therapy, closer monitoring, neurosurgical evaluation for hydrocephalus, or adjunctive therapies.(17)

Limitations

There are limitations: first, this is a single-centre observational study and causality cannot be firmly established. Second, the MRI burden score is novel and requires validation in external studys. Third, while we stratified by severity, long-term outcome data were not included here; thus, whether imaging findings predict outcome beyond severity at presentation remains to be studied.

In conclusion, this study demonstrates that in TBM, older age and multiple MRI abnormalities (basal meningeal enhancement, hydrocephalus, infarctions, cranial nerve involvement, parenchymal edema) are significantly associated with higher clinical severity. The findings reinforce earlier literature and provide quantified imaging–clinical linkage, which may help refine risk stratification and guide management in TBM.

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