British Infection Society guidelines for the diagnosis and treatment of tuberculosis of the central nervous system in adults and children

Summary and key recommendations

The aim of these guidelines is to describe a practical but evidence-based approach to the diagnosis and treatment of central nervous system tuberculosis in children and adults. We have presented guidance on tuberculous meningitis (TBM), intra-cerebral tuberculoma without meningitis, and tuberculosis affecting the spinal cord. Our key recommendations are as follows: 1. TBM is a medical emergency. Treatment delay is strongly associated with death and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of TBM is suspected. Do not wait for microbiological or molecular diagnostic confirmation. 2. The diagnosis of TBM is best made with lumbar puncture and examination of the cerebrospinal fluid (CSF). Suspect TBM if there is a CSF leucocytosis (predominantly lymphocytes), the CSF protein is raised, and the CSF:plasma glucose is <50%. The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with the volume of CSF submitted; repeat the lumbar puncture if the diagnosis remains uncertain. 3. Imaging is essential for the diagnosis of cerebral tuberculoma and tuberculosis involving the spinal cord, although the radiological appearances do not confirm the diagnosis. A tissue diagnosis (by histopathology and mycobacterial culture) should be attempted whenever possible, either by biopsy of the lesion itself, or through diagnostic sampling from extra-neural sites of disease e.g. lung, gastric fluid, lymph nodes, liver, bone marrow. 4. Treatment for all forms of CNS tuberculosis should consist of 4 drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months followed by 2 drugs (isoniazid, rifampicin) for at least 10 months. Adjunctive corticosteroids (either dexamethasone or prednisolone) should be given to all patients with TBM, regardless of disease severity. 5. Children with CNS tuberculosis should ideally be managed by a paediatrician with familiarity and expertise in paediatric tuberculosis or otherwise with input from a paediatric infectious diseases unit. The Children's HIV Association of UK and Ireland (CHIVA) provide further guidance on the management of HIV-infected children (www.chiva.org.uk). 6. All patients with suspected or proven tuberculosis should be offered testing for HIV infection. The principles of CNS tuberculosis diagnosis and treatment are the same for HIV infected and uninfected individuals, although HIV infection broadens the differential diagnosis and anti-retroviral treatment complicates management. Tuberculosis in HIV infected patients should be managed either within specialist units by physicians with expertise in both HIV and tuberculosis, or in a combined approach between HIV and tuberculosis experts. The co-administration of anti-retroviral and anti-tuberculosis drugs should follow guidance issued by the British HIV association (www.bhiva.org).

Introduction

Central nervous system (CNS) tuberculosis occurs in approximately 1% of all patients with active tuberculosis. It results from the haematogenous dissemination of Mycobacterium tuberculosis from primary pulmonary infection and the formation of small subpial and subependymal foci (Rich foci) in the brain and spinal cord.¹ In some individuals foci rupture and release bacteria into the subarachnoid space causing meningitis. In others, foci enlarge to form tuberculomas without meningitis.

The timing and frequency of these events in relation to primary pulmonary infection is dependent upon age and immune status. In children, dissemination usually occurs early and the risk of CNS tuberculosis is highest in the first year following infection¹; in high tuberculosis prevalence countries CNS tuberculosis predominantly effects very young children (<3years). In low tuberculosis prevalence countries such as the UK, most cases are in adults, often immigrants from areas of high tuberculosis prevalence.² Immune-suppressed adults, especially those with HIV infection, are more likely to suffer disseminated disease with CNS involvement.³ Other risk factors include alcoholism, diabetes mellitus, malignancy, corticosteroid treatment, and agents that block the action of tumour necrosis factor.⁴