Imaging manifestations of pediatric central nervous system tuberculosis in an endemic region

Abstract

Tuberculosis of the central nervous system is a deadly disease with a high mortality and morbidity rate. While tuberculosis is prevalent worldwide, most active cases are found in underdeveloped and developing countries, including Pakistan, where it is highly endemic. The pediatric population is particularly at high risk of developing CNS tuberculosis. This disease can manifest in various forms, such as tuberculous meningitis, tuberculoma, tubercular abscess, Pott’s spine, and tuberculous arachnoiditis. Given that the prognosis of CNS tuberculosis is closely tied to the stage at which treatment begins, it is crucial to make an early and accurate diagnosis using MRI.

In this case series, we present four pediatric patients who presented with a wide array of symptoms, ranging from fever and seizures to drowsiness.

The current study focuses on the radiological presentation of CNS tuberculosis in the pediatric population, with the hope that it may help address the gap in the lack of available case reports on CNS tuberculosis in Pakistan, an endemic country.

Introduction

Tuberculosis (TB), one of the most prevalent diseases worldwide, is primarily caused by a species of bacteria known as Mycobacterium tuberculosis [1]. Annually, approximately 1.5 million people succumb to TB, making it the second most common cause of death amongst infectious diseases [2].

Although TB is prevalent worldwide, most active cases are concentrated in underdeveloped and developing countries. Pakistan ranks among the nations where TB is highly endemic; it holds the dubious distinction of being the fifth-highest TB burden country in the world [3].

While most TB cases primarily affect the lungs, TB can also impact on the central nervous system (CNS), circulatory system, and lymphatic system [1]. CNS tuberculosis, although accounting for only 1–10% of all TB cases, carries the highest mortality and morbidity rates among all TB infections [4]. The pediatric population, in particular, face a heightened risk of developing CNS tuberculosis [5]. CNS tuberculosis can manifest in various forms including tuberculous meningitis, tuberculoma, tubercular abscess, Pott’s spine, and tuberculous arachnoiditis [4].

Given that the prognosis of CNS tuberculosis is closely linked to the stage of disease at which treatment commences, it becomes imperative to establish an accurate early diagnosis. Diagnosis is often challenging, especially due to the presence of abnormal neurological manifestations. However, imaging plays a pivotal role in achieving early diagnosis, with techniques like MRI being particularly useful in the visualization and evaluation of infarcts, tuberculomas, leptomeningeal enhancement, edema, ventricular dilatation, and other pertinent findings [4,6,7].

Case series

Case I

A five-year-old female with a known case of disseminated TB presented with a single episode of generalized tonic-clonic seizures and a one-day history of fever.

On examination, the child appeared lethargic and unwell. Examination of the chest and cardiovascular system revealed no significant findings. CNS examination showed intact function with a Glasgow Coma Scale (GCS) score of 15/15. Abdominal examination revealed tenderness in the right hypochondrial region.

A lumbar puncture was performed, and second-line anti-tuberculosis treatment (ATT) was initiated due to abnormal liver function tests, along with the addition of steroids.

A subsequent MRI scan revealed the presence of multiple abnormal signal intensity foci in both the supratentorial and infratentorial brain parenchyma. These foci appeared isointense to hypointense on T2 images and demonstrated isointense signals on T1-weighted images. Post-contrast images displayed rim enhancement. Associated perilesional vasogenic edema was also noted. Additionally, diffuse meningeal enhancement, most prominent at the basal cisterns, was observed. These findings were consistent with the presence of multifocal supratentorial and infratentorial tuberculomas (Fig. 1).

Fig. 1.

(A) Axial T2-weighted MRI, (B) Susceptibility-weighted image (SWI), (C) Axial post-contrast T1-weighted image, and (D) Sagittal post-contrast T1-weighted image demonstrate multifocal supratentorial and infratentorial tuberculomas (arrows), showing T2 hypointensity, signal dropout on SWI, and ring enhancement on post-contrast sequences. (E, F) Coronal post-contrast FLAIR images show diffuse meningeal enhancement, most prominent at the basal cisterns (arrowheads).

Case II

An 11-year-old male presented to the emergency department with fever and altered mental status for seven days. On examination, the patient exhibited drowsiness, with a Glasgow Coma Scale (GCS) score of 12/15. There was a very brisk response observed in deep tendon reflexes.

The child was admitted under the care of neurosurgery, and an external ventricular drain (EVD) was placed. A detailed analysis of cerebrospinal fluid (CSF) revealed an elevated total leukocyte count (TLC), high protein levels, and low glucose levels. The CSF Gene Xpert test detected Mycobacterium tuberculosis complex, leading to the diagnosis of CNS tuberculosis.

Antituberculosis therapy was initiated, along with oral Prednisolone. A ventriculoperitoneal shunt was also placed. On the 11th day of admission, the child developed right-sided focal seizures, a progressively declining GCS, and persistent tachycardia. An EEG revealed diffuse theta and delta slowing.

MRI showed multifocal vasculitis infarcts in the supratentorial brain parenchyma. Mild dilatation of the ventricular system was also noted, along with diffuse leptomeningeal enhancement involving bilateral optic nerves, basal and perimesencephalic cisterns, interpeduncular and prepontine cisterns, and the tentorium cerebelli (Fig. 2). Multiple infratentorial ring-enhancing lesions involving both cerebellar hemispheres, representing tuberculomas, were also observed.

Fig. 2.

(A, B) DWI and corresponding ADC images showing multifocal vasculitic infarcts involving the genu of the corpus callosum and right basal ganglia (arrows). (C, D) Post-contrast T1-weighted sagittal and axial images demonstrating diffuse leptomeningeal enhancement (arrowheads) involving the basal and perimesencephalic cisterns, interpeduncular and prepontine cisterns, and bilateral optic nerves.

Due to the persistently low GCS, a repeat CT scan was performed, which showed transependymal seepage of CSF with increasing hydrocephalus and diffuse cerebral edema. A neurosurgery consult was generated, and exteriorization of the ventriculoperitoneal shunt was performed, followed by placement of an EVD in the left lateral ventricle.

Case III

A 4-year-old male presented to the emergency department with fever persisting for over two weeks, vomiting for the past two days with four episodes, and a seizure episode. On examination, the patient appeared dull and lethargic, tachycardic, tested positive for neck stiffness, and exhibited positive clonus, along with right-eye ptosis. The Glasgow Coma Scale (GCS) score on presentation was 15/15.

On the eighth day of admission, the patient experienced generalized tonic-clonic seizures and was treated with IV Lerace and IV Diazepam. A lumbar puncture was performed to collect a sample of cerebrospinal fluid (CSF), which revealed elevated total leukocyte count (TLC) and the presence of mycobacteria. This led to the diagnosis of CNS tuberculosis.

The patient was transferred to the pediatric intensive care unit (PICU), where the GCS score decreased to 6/15, necessitating intubation. Antituberculosis therapy (ATT) was initiated, and due to raised intracranial pressure (ICP) issues, the neurosurgery team recommended shunt placement.

The child was successfully extubated and placed on high-flow oxygen, which was gradually tapered, resulting in an improvement in the child's GCS

On diffusion-weighted imaging (DWI), areas of diffusion restriction were observed in the left genu of the corpus callosum, left basal ganglia, posterior limb of the left internal capsule, and bilateral frontal white matter, corresponding to T2/FLAIR hyperintense signals and representing acute infarcts. Communicating hydrocephalus was noted. Nodular post-contrast enhancement was observed along the bilateral optic nerves, optic chiasm, and bilateral medial frontal lobes. These findings were indicative of tuberculous meningitis with multifocal vasculitic infarcts (Fig. 3).

Fig. 3.

(A, B) DWI and corresponding ADC images showing multifocal vasculitic infarcts in the left genu of the corpus callosum and left basal ganglia (arrows). (C) Post-contrast FLAIR coronal image and (D) post-contrast T1-weighted axial image demonstrating enhancement of the optic nerves and chiasm (arrowheads).

Case IV

A 14-year-old female patient presented to the ER with a one-week history of headache and pyrexia, vomiting for four days, and painful urination for three days. On examination, no significant findings were observed. A lumbar puncture was performed, which revealed tuberculous meningitis, leading to the initiation of anti-tuberculous therapy (ATT). The patient also developed cerebral salt wasting, for which hypertonic saline was administered.

Imaging revealed a focal area of diffusion restriction in the splenium of the corpus callosum, representing an acute infarct. Thickening and enhancement of the meninges were most pronounced in the posterior fossa and basal region. Perineural enhancement along bilateral facial and vestibulocochlear nerve complexes was observed. At least two ring-enhancing lesions were noted, one in the left occipital lobe and another along the left inferior-lateral aspect of the fourth ventricle. Diffuse brain edema was present, accompanied by mild hydrocephalus (Fig. 4).

Fig. 4.

(A, B) DWI and corresponding ADC images showing an acute infarct in the splenium of the corpus callosum (arrow). Mild hydrocephalus is also noted. (C, D) Post-contrast T1-weighted axial images demonstrating basal meningeal enhancement and perineural enhancement along the bilateral facial and vestibulocochlear nerve complexes (arrowheads). (E, F) Post-contrast T1-weighted sagittal images showing ring-enhancing lesions (broad arrows).

Discussion

Tuberculous Meningitis (TBM) is more prevalent in the Western world and typically presents with malaise, fever, headache, altered mental state, and neurological signs, often progressing to coma and death within five to eight weeks of onset. While Mycobacterium tuberculosis is the causative agent of Tuberculosis Meningitis, it should not be mistaken for Neisseria meningitidis, which is the most common causative agent of other forms of meningitis.

Neuroradiological findings of the infection can vary based on their location and the necrotic state of their center, which can be liquefactive central caseating or solid caseating, observed in 10% of tuberculomas. Imaging hallmarks of Tuberculosis Meningitis include hydrocephalus, granuloma or abscess formation, infarction, ventriculitis/vasculopathy, extra-axial collections, leptomeningeal and perineural enhancement [1,8].

When comparing our neuropathological findings with published literature on clinical and imaging manifestations of tuberculosis in the pediatric population, several studies reported similar patterns. Taheri et al. noted multiple focal or unifocal lesions, which were also seen in our patients.

On non-enhanced CT scans, granulomas may appear isodense, hyperdense, or of mixed density [6]. Bernaerts et al. described a triad of radiological manifestations, including basal meningeal enhancement, hydrocephalus, and infarctions in the supratentorial brain parenchyma and brain stem [9]. These findings correspond with our observed basal meningeal and perineural enhancements, leptomeningeal multifocal enhancements, and multiple infratentorial ring-enhancing lesions involving both cerebellar hemispheres [9].

A signal dropout pattern on ADC indicated infarction and limited perfusion, likely resulting from disturbed hemodynamics due to restricted arterial pulsation, as suggested by Bernaerts et al. Ischemic infarctions, primarily involving the basal ganglia and internal capsule regions, have been reported in 20%-41% of patients, including those in our study [6].

Infratentorial tuberculomas were also observed in our pediatric patients. Furthermore, our study revealed the involvement of cranial nerves, which may result from the diffuse leptomeningeal inflammation characteristic of tuberculous meningitis. The inflammatory response produces thick, gelatinous exudates, allowing direct infiltration of Mycobacterium tuberculosis into the cranial nerves and adjacent structures. Additional contributing mechanisms may include mass effect from tuberculomas, late-stage fibrotic changes, or interruption of vascular supply. Communicating hydrocephalus remains the most common manifestation of TB meningitis. It occurs due to impaired absorption of cerebrospinal fluid (CSF) at the arachnoid villi caused by thick, gelatinous inflammatory exudates, rather than obstruction of the ventricular system itself, as seen in obstructive (non-communicating) hydrocephalus [10]. Cherion reported optic nerve involvement, such as optic nerve granuloma, compression of the optic chiasm, or optochiasmatic arachnoiditis, which we also identified as optic chiasm and nerve enhancement [11].

While much of the literature aligns with our findings, some differences were noted. Approximately 10% of tuberculomas have been reported to exhibit central calcification, the “specific target sign,” [7] which was not seen in our patients. Supratentorial tuberculomas are more common in adults, whereas infratentorial lesions predominate in children; however, our adolescent cases demonstrated both patterns. Another study described spinal tuberculous meningitis characterized by cerebrospinal fluid loculations, obliteration of the spinal subarachnoid space, and loss of visible spinal cord in the cervicothoracic region, suggesting progressive degeneration of the spinal cord [12]. These features were not present in our cases.

In the differential diagnosis of CNS tuberculosis, it is crucial to consider other common intracranial infections, as cerebrospinal fluid (CSF) analysis can show overlapping features such as pleocytosis and elevated protein. Neuroimaging, however, often provides critical distinguishing clues. Pyogenic abscesses, commonly caused by Staphylococcus aureus and Streptococcus pneumoniae, typically appear on MRI as well-defined ring-enhancing lesions with a thin, smooth wall. The capsule is often T1 hyperintense and demonstrates restricted diffusion on DWI (Diffusion-Weighted Imaging) in the central cavity, which is a hallmark feature [13]. Conversely, fungal infections, such as those caused by Aspergillus or Candida species, may present with more heterogeneous imaging patterns. Fungal abscesses often have thicker, irregular walls with nodular or shaggy enhancement ². They may demonstrate intracavitary projections and are more likely to be multifocal. Furthermore, restricted diffusion on DWI within a fungal abscess can be variable and less consistent than in bacterial abscesses [14]. The presence of associated hemorrhagic components, particularly in the context of angioinvasive fungi like Aspergillus, is another key differentiator [15]. Therefore, while CSF findings may be nonspecific, a meticulous assessment of enhancement pattern, wall characteristics, DWI signals, and associated parenchymal changes on MRI can significantly narrow the differential diagnosis and guide appropriate antimicrobial therapy.

The reviewed studies provide valuable insight into the variation in clinical presentations and their associated radiological findings. Recognizing these differing imaging manifestations across case studies can help clinicians make timely and accurate diagnoses, particularly in resource-limited settings [5]. Delay in diagnosis and treatment may lead to debilitating or fatal outcomes [16].

Despite our best efforts to present these cases comprehensively, this study has limitations. Data were derived from a single healthcare facility, and several parameters could not be assessed, limiting generalizability. Variability in staff training and imaging technology may also influence findings. Nonetheless, these results contribute important data on imaging manifestations of CNS tuberculosis in an endemic region where literature remains scarce.

Conclusion

In conclusion, this case series of four patients posits valuable data for local doctors, and a unique piece of referential information for the global healthcare community. When compared with both conflicting and coinciding results from the available literature, stark differences can be drawn between common findings on imaging modalities with respect to the endemic region of interest. We hope that this data can contribute to bridging the gap in the available case reports on CNS tuberculosis in the pediatric population in Pakistan. Moreover, it may offer valuable insights into the diagnosis and management of this condition, ultimately benefiting patient care.

use of artificial intelligence (AI)-assisted technology for manuscript preparation

The authors confirm that there was no use of generative AI or artificial intelligence (AI)-assisted technologies for writing or editing of the manuscript and no images were manipulated using AI.

Patient consent

Written informed consent from the patients for publication has been obtained.