Discuss the pathogenesis, clinical features, investigations and management of tuberculous meningitis.

Introduction

Tuberculous meningitis (TBM) is the most devastating form of extrapulmonary tuberculosis, carrying high mortality and a high rate of permanent neurological sequelae. It is common in India, particularly in children and in HIV-infected adults. Outcome depends almost entirely on how early treatment is started — which is why treatment must begin on clinical suspicion.

Pathogenesis

1. Haematogenous dissemination of *Mycobacterium tuberculosis* during primary infection seeds subpial and subependymal foci — "Rich foci".

2. Later rupture of a Rich focus into the subarachnoid space releases bacilli and antigen.

3. A thick gelatinous exudate forms, most dense at the base of the brain, producing the three cardinal complications:

• Obstruction of CSF flow → communicating hydrocephalus
• Entrapment of cranial nerves at the skull base → palsies (especially VI, then III, IV, VII)
• Obliterative endarteritis of penetrating vessels → infarction (typically basal ganglia and internal capsule), causing hemiplegia and movement disorders

CLINICAL FEATURES — THREE STAGES (British Medical Research Council)

Key features:

• Subacute onset over weeks — the contrast with the hours-to-days onset of pyogenic meningitis, and the most useful discriminating history.
• Cranial nerve palsies — VI nerve commonest, then III, IV and VII.
• Hydrocephalus with headache, vomiting, papilloedema and deteriorating consciousness.
• Stroke from vasculitis — hemiparesis, movement disorders.
• Hyponatraemia — from SIADH or cerebral salt wasting; common and contributes to obtundation.
• Tuberculoma — focal mass lesion with seizures or focal deficit.
• Spinal arachnoiditis — radicular pain, paraparesis, sphincter disturbance.
• Look for evidence of TB elsewhere — pulmonary, lymph node, miliary; and for choroid tubercles on fundoscopy, which are pathognomonic when present.

Investigations

Lumbar puncture is the key investigation (after imaging where there is focal deficit, papilloedema or depressed consciousness):

• CBNAAT (Xpert MTB/RIF Ultra) on CSF — rapid, gives rifampicin resistance status; the recommended first test, though a negative result does not exclude TBM.
• AFB smear and mycobacterial culture — culture is the gold standard but takes weeks; send a large volume of CSF (at least 6 mL) and examine repeatedly to improve yield.
• CSF ADA — supportive; not specific.
• Neuroimaging (contrast CT or MRI): basal meningeal enhancement (highly characteristic), hydrocephalus, infarcts in the basal ganglia and internal capsule, and tuberculomas with ring enhancement.
• Supporting evidence of TB: chest X-ray (miliary or primary complex), sputum and gastric aspirate for AFB, Mantoux (often negative — anergy), lymph node FNAC, HIV testing, and serum sodium.

Management

1. Antitubercular therapy — start on clinical suspicion; do not wait for culture

An intensive phase with four drugs, followed by a prolonged continuation phase. Total duration is longer than for pulmonary TB — typically 9–12 months. CNS penetration differs between drugs: isoniazid, pyrazinamide and ethionamide penetrate well; rifampicin and streptomycin penetrate poorly and ethambutol least, which shapes regimen design.

2. Corticosteroids — proven to reduce mortality

Adjunctive dexamethasone or prednisolone reduces death in all stages and should be given to every patient, tapered over 6–8 weeks. This is one of the few interventions in neuro-infection with clear mortality benefit and is a high-yield examination point.

3. Management of complications

• Hydrocephalus: serial monitoring; ventriculoperitoneal shunt or external ventricular drain for obstructive hydrocephalus with deteriorating consciousness; acetazolamide and furosemide have a limited role in communicating hydrocephalus.
• Raised intracranial pressure: head elevation, mannitol, avoidance of hypotonic fluids.
• Seizures: antiepileptic drugs — note interaction between phenytoin/carbamazepine and rifampicin.
• Hyponatraemia: distinguish SIADH (fluid restriction) from cerebral salt wasting (salt and volume replacement — fluid restriction here is harmful).
• Pyridoxine with isoniazid to prevent peripheral neuropathy.
• Paradoxical reaction — clinical or radiological worsening on treatment from immune reconstitution; managed with steroids, not by stopping ATT.

4. HIV co-infection

Screen every patient. ATT is started first, with ART deferred by a few weeks in TBM specifically, because early ART increases the risk of fatal IRIS in this setting — unlike other forms of TB where early ART is favoured.