Diagnosis: disseminated tuberculosis (TB).
MRI of the brain with gadolinium enhancement revealed multiple bilateral small supratentorial and infratentorial lesions, as well as large conglomerated left parasaggital enhancing lesions with edema (figure 1); findings were reported as being compatible with cysticercosis, bacterial brain abscesses, tuberculomas, or metastases. The chest radiograph revealed bilateral alveolar and interstitial densities in a milary pattern with left perihilar lymphadenopathy (figure 2).
MRI of the brain with contrast enhancement showing multiple bilateral small supratentorial (top left arrow) and infratentorial (bottom arrow) lesions, as well as large conglomerated left parasagittal enhancing lesions (top right arrow) with edema.
MRI of the brain with contrast enhancement showing multiple bilateral small supratentorial (top left arrow) and infratentorial (bottom arrow) lesions, as well as large conglomerated left parasagittal enhancing lesions (top right arrow) with edema.
Chest radiograph showing alveolar and interstitial densities with a miliary pattern and left perihilar lymphadenopathy (arrow).
Chest radiograph showing alveolar and interstitial densities with a miliary pattern and left perihilar lymphadenopathy (arrow).
A clinical diagnosis of miliary TB was made, and the patient initiated therapy with isoniazid, rifampin, pyrazinamide, and ethambutol. A TB skin test had positive results, with an induration that was 14 mm in diameter. Direct smears of 2 of 3 gastric lavage fluid samples had results positive for acid-fast bacilli, but PCR of the samples had results that were negative for TB. However, cultures of the samples ultimately grew pansusceptible Mycobacterium tuberculosis. Lumbar puncture was not performed because of the risk of complications and because it would not alter the treatment plan. Prednisolone was added to the patient's regimen during the second week of therapy and was continued for 1 month for presumptive CNS TB.
This patient's diagnosis became clear only after the chest radiograph was obtained. Primary TB in childhood is frequently a difficult diagnosis to make, because the mainstay of diagnosis is sputum smear microscopy, and sputum samples cannot readily be obtained from young children. Thus, accurate interpretation of the chest radiograph assumes great importance. In this case, the persistent CNS symptoms were not suspected to be due to TB, because the patient remained seizure-free for 1 month while receiving anticonvulsants, and because CT of the brain had normal findings. Headache and vomiting in the absence of fever were suggestive of a space-occupying lesion, but the normal findings of a CT scan of the brain also made this diagnosis unlikely. We suspect that the brain CT had normal findings (despite the florid findings of the MRI obtained 4 weeks later) because the multiple tuberculomas were too small to be visualized on CT without contrast at that point (although they would almost certainly have been visible on CT with contrast or on MRI) [1].
The similarities in neuroimaging findings with neurocysticercosis and multiple intracranial tuberculomas have been previously described [2], and the single seizure, combined with the appearance of the patient's MRI of the brain, was suspicious for neurocysticercosis, which can occur in northern Iran. However, neurocysticercosis would not account for the miliary pattern on the chest radiograph. Advanced malignancy could account for all clinical features and imaging abnormalities in this case, but it would be more likely in an adult than in a child. Biopsy of tuberculomas because of suspected malignancy is relatively common in countries where TB is endemic [3].
The role of PCR in the diagnosis of TB is not clear, because results depend on the bacterial load [4]. Therefore, in a paucibacillary situation, such as PCR of a gastric aspirate sample from a child, a negative result is not surprising. The usefulness of PCR and TB antigen detection tests [5] of CSF samples for diagnosis of TB meningitis requires further study.
During primary TB infection, bloodstream dissemination can occur, with seeding of all organ systems. CNS infection can present as 1 or multiple tuberculomas, basal arachnoiditis, or meningoencephalitis (which is thought to occur as the result of rupture of a subependymal tuberculoma). Tuberculomas are more commonly evident on neuroimaging in adults than in children [6]. One or more tuberculomas in association with TB meningitis was reported in 34 of 202 children from South Africa for whom CT of the brain was performed. The most common finding was a single meningeal tuberculoma [7], although, with improvements in neuroimaging, it is likely that more lesions would have been evident in some cases [1]. Only 4 of the 34 children had neuroimaging findings similar to those for our patient, with multiple small parenchymal lesions [7]. It is postulated that these imaging findings are in keeping with miliary TB; indeed, these 4 patients and our patient all had chest radiograph findings compatible with miliary disease. In a study involving 102 adults and children with tuberculomas, common presenting features included fever (in 59% of cases), headache (57%), and meningeal irritation (36%), with the prognosis being worse if the patient presented with coma or had a miliary pattern visible on chest radiograph [8].
Intracranial tuberculomas generally resolve uneventfully with a 6-month course of TB therapy [7], although it remains common to complete a 12-month course. A paradoxical increase in the size of lesions after initiation of therapy has been reported [7, 9, 10]. This is sometimes associated with clinical deterioration, and the appropriate management is not yet clear [9, 10]. Development of hydrocephalus was reported in 38 (37%) of 102 adults and children with tuberculomas [8], so repeated neuroimaging is vital if there are any clinical signs of increased intracranial pressure during TB therapy. Corticosteroids have been shown to be effective in speeding resolution of intracranial tuberculomas in serial imaging studies [11]. In our patient, the CNS lesions had markedly improved after 1 month of corticosteroid therapy and 3 months of anti-TB therapy (figure 3).
MRI of the brain after 3 months of therapy for tuberculosis showing marked resolution of tuberculomas.
MRI of the brain after 3 months of therapy for tuberculosis showing marked resolution of tuberculomas.
Although the prevention of miliary and CNS TB is the main advantage of routine use of bacille Calmette-Guérin vaccine in developing countries [4], vaccine failure occurs [11]. An immunologic work-up to exclude a defect in cell-mediated immunity is recommended for children who experience failure of bacille Calmette-Guérin vaccination; in our case, the results of an immunologic work-up, including a phagocytosis assay, were normal.
Acknowledgments
Potential conflicts of interest.All authors: no conflicts.
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