A young woman with headache and vomiting

1. What is the most likely diagnosis?

Cerebral TB in the form of a tuberculoma is the most likely diagnosis. A progressively worsening headache, with “high pressure” features, such as being worse on lying flat/in the morning, and persistent vomiting suggest an intracranial lesion. A ring enhancing intracranial lesion on computed tomography in a patient with previously treated multidrug resistant TB (MDR TB), makes tuberculoma the most likely diagnosis.

Differential diagnoses include bacterial abscess, tumour (eg, ependymoma/haemangioblastoma), toxoplasmosis, or cysticercosis.

In the UK the rate of TB relapse following successful treatment is reported as around 0.4%.1 Central nervous system (CNS) TB (such as TB meningitis, CNS tuberculoma, and spinal TB) accounts for around 1% of all TB cases.2 Worldwide it is commonly seen in children; however, in areas of low TB prevalence, including the UK, most cases are seen in adults from areas of high TB prevalence.3

Tuberculomas account for 1% of CNS TB cases. There is more than one in 15-33% of cases.4 It is thought that haematological dissemination occurs at the time of primary pulmonary infection. Mycobacterium tuberculosis (MTB) crosses the blood-brain barrier and forms small subependymal and subpial foci, called “rich foci.”5 These foci undergo granulomatous reactions and gradually enlarge. If these foci rupture, M tuberculosis is spread into the subarachnoid layer leading to TB meningitis. If they do not rupture, they enlarge to form a tuberculoma.6 Delayed presentation of CNS TB has been reported, with suggestions that it may lie dormant for months to years.4

2. How is this diagnosis confirmed?

CNS TB is confirmed by analysis of cerebrospinal fluid. Microscopy identifies acid fast bacilli (AFB) in the fluid. Mycobacterium culture allows identification of MTB and enables drug sensitivity testing. If lumbar puncture is contraindicated, and therefore cerebrospinal fluid cannot be obtained, or if the cerebrospinal fluid cannot confirm diagnosis of TB, then a biopsy of the lesion with tissue culture and polymerase chain reaction may be performed.

Cerebral tuberculomas may be asymptomatic. Few produce focal neurological deficit. Generic features of raised intracranial pressure, such as headache, visual disturbance, and vomiting, may be present alongside systemic features such as fever and/or weight loss. Generalised and partial seizures can also be symptoms of cerebral tuberculomas.7

First line investigations include full blood screen, blood cultures, and chest radiography.

CNS tuberculomas are readily visualised on computed tomography and magnetic resonance imaging. Computed tomography with contrast generally reveals a well demarcated, lobular, ring enhancing lesion with surrounding oedema. MRI shows an isointense lesion on T1/T2 imaging, which ring-enhances with contrast.

Perform analysis of cerebrospinal fluid if it is not contraindicated. In CNS tuberculoma, analysis of cerebrospinal fluid frequently shows a pleocytosis, with lower rates of AFB detected.2

3. How would you manage this condition?

Standard “first line” TB treatment is recommended for those with CNS TB, with a reducing regimen of dexamethasone.28 Start rifampicin, isoniazid, pyrazinamide, and ethambutol. Contact the multi drug resistant (MDR) TB expert team in cases of previous MDR TB.2 Surgical resection of the tuberculoma, with or without a cerebrospinal fluid shunt, may be required to relieve any mass effect or hydrocephalus.

TB treatment guidelines are available from the National Institute for Health and Care Excellence and the British Infection Society.

The standard adult treatment regimen comprises an initial intense course of isoniazid (300 mg once daily), rifampicin (600 mg once daily, 450 mg <50 kg), pyrazinamide (2 g daily, 1.5 g <50 kg, maximum daily dose 2g) and ethambutol (15-20 mg/kg/day, maximum daily 1g), continued for two months. Pyrazinamide and ethambutol are stopped after the first two months of treatment, isoniazid and rifampicin continue for a further 10 months.2

Corticosteroid use has been shown to reduce mortality and morbidity in CNS TB.9 Treatment is normally with dexamethasone at a dose of 0.4 mg/kg/day, tapering over 6-8 weeks.

Consider the possibility of MDR TB before starting treatment. The incidence of MDR TB is rising and is around 3.3% of all new TB cases.10 Specific risk factors for MDR TB include previous TB treatment, an area with high prevalence of drug resistant TB and/or exposure to someone with drug resistant TB. Treatment of MDR CNS TB is based on limited evidence gained from treating MDR pulmonary TB. In cases where the patient is known to be at high risk for MDR TB consider genotyping for drug resistance.

Learning point

CNS TB may lie dormant for long periods in patients with previous TB. It frequently presents with non-specific symptoms and may not cause neurological deficits. A low index of suspicion and threshold for cranial imaging should be adopted in these patients. Multidisciplinary team management is recommended for these cases.

Patient outcome

The patient underwent posterior fossa craniotomy and excision of the tuberculoma. The tissue specimen was sent for tissue sampling and genetic analysis, because of previous drug resistance status. A drug regimen of moxifloxacin, pyrazinamide, cycloserine, meropenem, protionamide, coamoxiclav, and pyridoxine was started based on previous sensitivities and drug penetration into the central nervous system. The patient remained clinically well and has since been discharged on continuing treatment. Mycobacterial culture was positive and whole genome sequencing indicated that the isolate was similar to that isolated from sputum previously. No evidence of additional drug resistance was found.