Infection of the meninges with Mycobacterium tuberculosis.
It is seen in 1% of all cases of TB.
May occur at any age.
Rare in the developed world but a major problem in developing countries.
May arise as a complication of miliary tuberculosis or in primary or post primary infections. In the Western world, TB occurs most often as part of a reactivation process due to immune deficiency, e.g. secondary to ageing, alcoholism, HIV or immunosuppression. Tuberculous meningitis is rare after BCG vaccination.
If a tuberculous focus develops in the brain, meninges or skull and ruptures into the subarachnoid space, a hyper-sensitivity reaction occurs leading to intense inflammation. This inflammation can directly involve the cranial nerves, particularly at the base of the brain; it can lead to a vasculitis which causes strokes; and it can cause communicating hydrocephalus by impeding cerebrospinal fluid (CSF) flow and resorption.
The onset is usually insidious over days or weeks, although it may present as an acute illness.
Stage I: Vague headache, lassitude, anorexia and low-grade fever.
Stage II: Signs of meningism (headache, vomiting, confusion, neck stiffness). Focal neurology may develop at this time including cranial nerve signs and hemiparesis.
Stage III: Untreated, the patient becomes comatose.
The subarachnoid space is filled with a viscous green exudate, the meninges are thickened and tubercles and chronic inflammation may be seen in the brain and on the meninges.
A lumbar puncture should be performed and the CSF should be stained with Ziehl Nielson stain, and then undergo prolonged culture. The CSF is typically cloudy, with a predominance of mononuclear cells (250–500 lymphocytes/mm3) with raised protein and lowered glucose. Repeated LP cultures increase the diagnostic sensitivity, as a single sample is only positive in less than 50%.
CT and MRI imaging may demonstrate hydrocephalus and basilar meningeal enhancement – both together are strongly suggestive of TB, MRI may demonstrate a focal vasculitis.
Polymerase chain reaction (PCR) testing is useful but not reliable, with only 60% positive in proven cases.
In addition, suspected cases should be screened with a chest X-ray, sputum culture and in confirmed cases an HIV test should be performed.
A minimum of 12 months therapy with rifampicin and isoniazid supplemented by pyrazinamide and a fourth drug for at least the first 2 months is recommended. The fourth drug may be ethambutol or streptomycin but these only penetrate the CNS adequately in the early stages, whilst the meninges are inflamed. Treatment should be initiated on clinical suspicion, before confirmation, as deterioration can occur within days, and even when treated mortality is as high as 15–40%.
Corticosteroids have been shown to reduce vascular complications, and improve survival and neurological function. High dose prednisolone is used in cases with rapid progression, cerebral oedema, hydrocephalus or basilar enhancement on CT, with high levels of CSF protein (>0.5 g/L) and in cases where there is a clinical deterioration with the onset of therapy, due to the increase in inflammatory response which may occur.