Diagnostic challenges in cerebral tuberculoma presenting with seizures in pregnancy

Abstract

Tuberculoma is an uncommon presentation of tuberculosis and is found in regions with a high prevalence of tuberculosis. This is rarely diagnosed during pregnancy. The presentation can mimic other etiologies such as eclampsia or cerebral venous sinus thrombosis so the diagnosis can be challenging, particularly when presenting with seizures in pregnancy. Described here is a woman in her first pregnancy who presented with seizures mimicking eclampsia and was suspected to have a brain tumour on neuroimaging. She was diagnosed to have a intracerebral tuberculoma on histopathological examination following surgical decompression after delivery.

Introduction

Space occupying lesions (SOLs) in the brain presenting during pregnancy are very rare. ¹ Tuberculoma is a rare complication of tuberculosis, found in regions with a high prevalence of tuberculosis, and this constitutes about 20% of all intracranial SOLs in developing countries like India.^{2, 3} It may resemble a meningioma on clinical or radiological presentation. Here we describe the case of a pregnant woman who underwent craniectomy following caesarean section for a suspected brain tumour when she presented with seizures, and was later diagnosed with a cerebral tuberculoma.

Case report

A 22-year-old woman in her first pregnancy, was referred to the emergency department at 38 weeks of gestation, following a generalized tonic-clonic seizure. She was in the early stage of labour. As she did not have a previous history of seizures, a presumptive diagnosis of eclampsia was made and she was given a loading dose of magnesium sulphate. On reviewing the history, she revealed having an episode of numbness involving her right upper and lower limbs two weeks prior to presentation, which lasted for several hours. Her blood pressure in pregnancy had always been normal. She could not undergo detailed evaluation due to the non-availability of medical and imaging facilities and restriction for travel during the COVID pandemic. Her blood pressure was 133/80 mmHg at admission, and her spot urine protein evaluation was negative. Neurological examination revealed normal cognition, but grade 4/5 power in the right upper and lower limbs on motor examination. Sensation was normal. She was in active labour with 4/5 fetal poles palpable, and with cephalo-pelvic disproportion on pelvic examination. Within one hour of admission, she had two right-sided focal motor seizures with secondary generalization. She was started on intravenous levetiracetam. Due to logistic difficulties for performing immediate neuroimaging and her being in active labour, after discussion between the Neurology and the treating Obstetric team, an emergency caesarean section was performed in view of recurrent seizures and cephalon-pelvic disproportion. She delivered a live male baby weighing 3750 g, with a five-minute APGAR score of 8. Due to suspicion of cerebral venous sinus thrombosis or intracranial bleed, a computed tomographic (CT) venogram was performed in the postoperative period, which showed no evidence of dural venous sinus thrombosis. However, focal vasogenic oedema with mass effect and midline shift was noted, involving left frontal and parietal lobes. Post-contrast images showed sulcal enhancement with associated cortical thickening. A radiological differential diagnosis of leptomeningitis or a neoplastic lesion was given (Figure 1 A, B, C). She underwent emergency decompressive hemi-craniectomy with resection of abnormal tissue. She was continued on anti-epileptics (intravenous levetiracetam) and anti-edema (intravenous mannitol) measures postoperatively.

Figure 1.

A- Plain axial CT scan of the brain at supraventricular level shows focal vasogenic edema involving left frontoparietal lobes, B- plain axial CT image at the level of the frontal horn of lateral ventricles shows midline shift to the right side by 11 mm, C- contrast-enhanced CT at supraventricular level shows evidence of enhancement along the sulci with thickening of the adjacent cortex, involving left frontoparietal lobes. No evident intra-parenchymal enhancing focal lesion, D- non-contrast CT post decompression craniotomy shows resolution of midline shift.

Serial non-contrast CT scans in the postoperative period showed resolution of oedema and mass effect (Figure 1D). At discharge on the 9th postoperative day, she was advised to continue physiotherapy for the residual right-sided weakness. Histopathology showed numerous granulomatous lesions with occasional central necrosis, involving brain parenchyma and meninges, suggestive of tuberculoma (Figure 2). Tissue staining and culture for acid-fast bacilli and fungal organisms were negative. She was started on anti-tubercular therapy (ATT) after discussion with a tuberculosis programme officer. She recollected later that her father was diagnosed and treated for tuberculosis ten years previously. She has completed her intensive phase of ATT and is now in the continuation phase of treatment. On follow-up after 4 weeks, neurological examination showed some improvement.

Figure 2.

Microphotograph showing normal brain parenchyma (right side- black arrow) with coalescing granulomatous lesion composed of aggregates of epitheloid cells, Langhans-type giant cells and lymphocytes. X 200 H&E.

Discussion

Seizures occurring in the third trimester of pregnancy are commonly due to eclampsia. The availability of neuroimaging to differentiate eclampsia from other causes, such as cortical vein thrombosis with intracranial bleed and intracranial tumours, is limited to regional centres in most low to middle-income countries. Although tuberculoma is not uncommon in endemic areas, it can be easily misdiagnosed. It can present with similar clinical features to pregnancy-specific conditions, such as eclampsia, or those in which there is an increased risk in pregnancy including cerebral venous sinus thrombosis, aneurysmal rupture, intracranial tumours, or infective lesions (e.g. neuro-cysticercosis). ⁴ Post-primary dissemination, through the hematogenous route, is common among children and young adults in endemic regions, and extrapulmonary TB affecting the central nervous system is reported to occur in 10%.^2,3 Changes in the immune system during pregnancy may increase susceptibility to reactivation of latent TB, whilst simultaneously masking symptoms. One possible mechanism is the suppression of the proinflammatory Th1 response. Our patient may have contracted TB ten years previously, when her father was unwell, but only in the context of immunosuppression associated with pregnancy did the infection manifest for the first time. ⁵

The most frequent CNS manifestation of tuberculosis is meningitis, followed by tuberculoma and spinal arachnoiditis. Tuberculoma is a conglomerate granulomatous focus that develops from coalescing tubercles acquired during disseminated bacillemia and could be intraparenchymal or with dural involvement (pachymeningitis). Tuberculoma may resemble meningioma due to their well-circumscribed contours, often extra-axial location and dural attachment. Tuberculomas are more often noted in the frontal and parietal lobe, especially on the left, probably from greater blood flow to the dominant hemispheres. ⁶ They usually presents with headache, vomiting, visual disturbance, seizures, motor deficits depending on the precise location and the degree of raised intracranial pressure.^7,8 Our patient initially had transient motor symptoms, followed later by seizures. There were no constitutional or pulmonary symptoms to suggest underlying tuberculosis.

Diagnosis of tuberculoma preoperatively requires a strong suspicion and is highly challenging, especially when there are no extracranial tuberculosis foci. In this woman, the neuroimaging was delayed for several reasons including (i) availability of neuroimaging and other facilities were limited to regional centres, (ii) restriction in travel (because of lockdown from COVID pandemic) made it difficult to travel from smaller villages/ towns and (iii) the fear of contracting COVID from the hospital might have also contributed to the delay. Definitive radiological diagnosis of tuberculoma is not possible as there are no features which are 100% specific. Furthermore, imaging appearances change over time as the lesions evolve. Tuberculomas are seen as single or multiple discrete, ring-enhancing lesions of the brain surrounded by perilesional edema on computed tomography. In contrast-enhanced CT images, early-stage tuberculomas are seen as low density or iso-dense lesions with edema out of proportion to mass effect and with little encapsulation, while in later stages, they are well encapsulated, iso-dense, or hyperdense and have peripheral ring enhancement^7,8 while meningiomas are usually iso-dense to hyperdense on CT scan. Other investigations like the Mantoux test, acid-fast stains, chest radiography, culture, and PCR are neither specific nor sensitive.^9–12 As in this case, pathological diagnosis is the gold standard, enabling the correct treatment to be provided.

Tuberculomas can be managed medically with ATT, but if there are symptoms suggestive of increased intracranial pressure, midline shift, or those which didn’t respond to ATT, surgery is the treatment of choice. Treatment of tuberculoma with ATT can promptly result in the resolution of symptoms without any residual deficits.

Conclusion

Although rare in pregnancy, intracranial tuberculoma should be taken into consideration in the differential diagnosis of individuals presenting with atypical seizures (for example, focal rather than generalized tonic-cloinc) and intracranial space-occupying lesions, especially in the regions with a high prevalence of tuberculosis.