Tuberculous meningitis

Tuberculous meningitis is also known as "TB meningitis".

Tuberculous meningitis is Mycobacterium tuberculosis infection of the meninges. It is the most common form of CNS tuberculosis.

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Clinical features

Fever and headache are the cardinal features. Confusion is a late feature and coma bears a poor prognosis. Meningism is absent in a fifth of patients with TB meningitis. Patients may also have focal neurological deficits.

Pathology

Mycobacterium tuberculosis of the meninges is the cardinal feature and the inflammation is concentrated towards the base of the brain. Infection begins in the lungs and may spread to the meninges by a variety of routes.

Blood-borne spread certainly occurs and 25% of patients with miliary TB have TB meningitis, presumably by crossing the blood-brain barrier^[1]; but a proportion of patients may get TB meningitis from rupture of a cortical focus in the brain (a so-called Rich focus); an even smaller proportion get it from rupture of a bony focus in the spine. It is rare and unusual for TB of the spine to cause TB of the central nervous system, but isolated cases have been described.

Diagnosis

Diagnosis of TB meningitis is made by analysing CSF collected by lumbar puncture. When collecting CSF for suspected TB meningitis, a minimum of 1ml of fluid should be taken (preferably 5 to 10ml).

The CSF usually has a high protein, low glucose and a raised number of lymphocytes. Acid-fast bacilli are sometimes seen on a CSF smear, but more commonly, M. tuberculosis is grown in culture. A spiderweb clot in the collected CSF is characteristic of TB meningitis, but is a rare finding.

More than half of cases of TB meningitis cannot be confirmed microbiologically, and these patients are treated on the basis of clinical suspicion only. The culture of TB from CSF takes a minimum of two weeks, and therefore the majority of patients with TB meningitis are started on treatment before the diagnosis is confirmed.

Nucleic acid amplification tests (NAAT)

This is a heterogeneous group of tests that use polymerase chain reaction (PCR) to detect mycobacterial nucleic acid. These test vary in which nucleic acid sequence they detect and vary in their accuracy. The two most common commercially available tests are the amplified mycobacterium tuberculosis direct test (MTD, Gen-Probe) and Amplicor. In 2007, a systematic review of NAAT by the NHS Health Technology Assessment Programme concluded that for diagnosing tuberculous meningitis "Individually, the AMTD test appears to perform the best (sensitivity 74% and specificity 98%) [page 87]" ^[2]. In the NHS meta-analysis, they found the pooled prevalence of TB meningitis to be 29% [page 85]; however there was much heterogeneity in the reported sensitivities. Using a clinical calculator, these numbers yield a positive predictive value of 94% and a negative predictive value of 90%; however the 30% prevalence may be high due to referral bias. Alternate estimates of disease prevalence can be entered into the clinical calculator to refine the predictive values.

Imaging

Imaging studies such as CT or MRI may show features strongly suggestive of TB meningitis, but cannot diagnose it.

Treatment

See: tuberculosis treatment

The treatment of TB meningitis is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, followed by isoniazid and rifampicin alone for a further ten months. Steroids are always used in the first six weeks of treatment (and sometimes for longer). A few patients may require immunomodulatory agents such as thalidomide.

Treatment must be started as soon as there is a reasonable suspicion of the diagnosis. Treatment must not be delayed while waiting for confirmation of the diagnosis.

Hydrocephalus occurs as a complication in about a third of patients with TB meningitis and will require a ventricular shunt.

References

1. ^ Jain SK, Paul-Satyaseela M, Lamichhane G, et al. (2006). "Mycobacterium tuberculosis invasion and traversal across an invitro human blood-brain barrier as a pathogenic mechanism for central nervous system tuberculosis". J Infect Dis 193 (9): 1287–95.
2. ^ Dinnes J, Deeks J, Kunst H, Gibson A, Cummins E, Waugh N, Drobniewski F, Lalvani A (2007). "A systematic review of rapid diagnostic tests for the detection of tuberculosis infection". Health Technol Assess 11 (3): 1-314. PMID 17266837.