Tuberculous meningitis

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Mycobacterium tuberculosis reaches the CNS haematogenously after primary or reactivated infection and establishes small subpial or subependymal foci. Rupture into the subarachnoid space produces a dense basal exudate. Disease can occur without obvious pulmonary symptoms, and CSF contains few organisms, making microbiological confirmation difficult.

Basal inflammation obstructs CSF flow, encases cranial nerves and inflames perforating arteries, producing hydrocephalus, neuropathies and infarction. Treatment must begin before culture confirmation when clinical probability is substantial. Prolonged multidrug therapy addresses slow bacillary clearance, while dexamethasone reduces inflammatory death and disability and neurosurgery treats mechanical hydrocephalus.

Key points

TB meningitis usually evolves over days to weeks with headache, fever, malaise, weight loss, cranial neuropathy or cognitive decline.
CSF commonly shows lymphocytes, high protein and low glucose, but early neutrophils and immune-suppressed low-cell profiles occur.
Send a large CSF volume for mycobacterial culture and molecular testing and repeat sampling when initial tests are negative but probability remains high.
MRI best demonstrates basal enhancement, hydrocephalus, infarction and tuberculoma; chest imaging and sputum can provide an easier culture and susceptibility source.
Start treatment on clinical probability because smear and rapid molecular sensitivity are limited in paucibacillary CSF disease.
Use current UK weight-banded rifampicin, isoniazid, pyrazinamide and ethambutol for 2 months followed by rifampicin and isoniazid to complete about 12 months.
Give adjunctive dexamethasone with a staged taper for TB meningitis unless a specialist contraindication exists.
Test HIV and coordinate ART timing, rifamycin interactions and immune-reconstitution risk through a TB-HIV team.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Haematogenous M tuberculosis

Bacilli spread from pulmonary or other infection to small CNS foci that later rupture into CSF and meninges.

Reactivation and immune risk

HIV, malnutrition, immunosuppression, recent exposure and migration from high-incidence settings increase disease progression and can substantially alter clinical presentation.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Basal exudative inflammation
Dense inflammatory material accumulates around brainstem cisterns, encasing cranial nerves and progressively obstructing normal CSF circulation pathways.
2
Meningovascular infarction
Inflammation of perforating arteries causes thrombosis and basal-ganglia or brainstem infarcts with persistent focal neurological disability.
3
Tuberculoma formation
Granulomatous masses produce focal seizures and oedema and can enlarge paradoxically after otherwise effective antituberculous therapy begins.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Subacute basal meningitisRed flag

Weeks of headache, fever, vomiting, lethargy and weight loss with neck stiffness or cranial neuropathy is a typical presentation.

HydrocephalusRed flag

Worsening headache, sixth-nerve palsy, papilloedema and declining consciousness suggests obstructed CSF flow.

Meningovascular diseaseRed flag

Focal weakness, dysphasia or movement disorder indicates perforator infarction from basal vasculitis.

Paradoxical tuberculomaRed flag

New focal signs or enlarging lesions after initial treatment may be inflammatory paradox rather than resistance, but both require assessment.

Red flags requiring action

Reduced consciousness, papilloedema, repeated vomiting or sixth-nerve palsy raises hydrocephalus and requires urgent neuroimaging and neurosurgical review.
Focal deficit or seizure may reflect basal-artery vasculitis and infarction rather than simple meningeal irritation.
A negative CSF PCR or smear does not exclude TB meningitis and must not postpone treatment when the syndrome is convincing.
Hyponatraemia requires volume assessment because SIADH and cerebral salt wasting have different fluid implications.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
High-volume CSF mycobacterial studiesFirst step
Why
Maximise smear, culture and molecular diagnostic yield.
Interpretation and limitations
Send the largest safe volume for Xpert or local NAAT, smear and prolonged culture; one negative result is insensitive and repeat sampling can be decisive.
02
CSF cells, glucose and protein
Why
Support chronic meningitis and track complications.
Interpretation and limitations
Lymphocytes, very high protein and low glucose are typical but not specific; early neutrophils or immune-suppressed paucicellular CSF do not exclude TB.
03
MRI brain and spine
Why
Map basal enhancement, hydrocephalus, infarction, tuberculoma and spinal arachnoid disease.
Interpretation and limitations
MRI is most sensitive; urgent CT may identify hydrocephalus before lumbar puncture when pressure or mass effect is suspected.
04
Extraneural TB microbiology
Why
Find a safer, higher-yield source and obtain susceptibility.
Interpretation and limitations
Chest imaging, sputum, node, urine or other tissue culture can confirm TB and resistance even when CSF remains negative.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Cryptococcal meningitis

Subacute headache, raised pressure and low glucose overlap, especially in HIV; antigen and fungal culture distinguish disease.

Carcinomatous or inflammatory meningitis

Malignancy, sarcoidosis and autoimmune disease can cause chronic lymphocytic low-glucose CSF, cranial neuropathy and progressive neurological decline.

Partially treated bacterial infection

Prior antibiotics can produce lymphocytic or culture-negative CSF, requiring bacterial molecular testing and careful review for an extracranial source.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01ASSESSDiagnose without false reassuranceFirst stepSubacute meningitis with low glucose, cranial neuropathy or TB exposure creates significant probability.

1Stabilise physiology, examine cranial nerves and focal neurology and obtain urgent imaging before lumbar puncture when mass effect is plausible.
2Collect high-volume CSF and multiple extraneural specimens for molecular tests, culture and susceptibility before therapy when safe.
3Test HIV and record weight, vision, renal, liver, sodium and all interacting medicines and pregnancy status.
4Start treatment and dexamethasone on probability; do not await culture when delay risks irreversible CNS injury.

02TREATStart prolonged multidrug therapyTB meningitis is confirmed or remains strongly suspected after samples are collected.

1Use the current UK weight-banded four-drug intensive regimen for 2 months, then rifampicin and isoniazid to complete approximately 12 months.
2Provide pyridoxine with isoniazid when neuropathy risk or local protocol indicates and monitor ethambutol visual safety.
3Give dexamethasone at stage-appropriate dose with a gradual specialist taper and adjust for rifampicin interaction.
4Coordinate ART timing and rifamycin-compatible regimen in HIV, usually avoiding the immediate start used for uncomplicated infections.

03REVIEWManage inflammation and sequelaeHydrocephalus, infarction, tuberculoma or deterioration occurs during treatment.

1Drain hydrocephalus through external, ventricular or shunt strategies when neurosurgical criteria are met; medicines cannot correct severe obstruction alone.
2Re-image new deficits or deterioration and assess adherence, exposure, resistance, infarct, hydrocephalus and paradoxical inflammation together.
3Use culture and susceptibility to modify resistant disease and avoid adding a single drug to an inadequate regimen.
4Arrange prolonged neurological, endocrine, visual, hearing, cognitive and rehabilitation follow-up and complete public-health contact work.

Key medicines and prescribing safety3 treatments · regimens, roles and cautions

Provides multidrug treatment before susceptibility is known and reduces resistance selection.

Initial TB meningitis regimen

Give weight-banded rifampicin, isoniazid, pyrazinamide and ethambutol daily for 2 months under current NICE and TB-service guidance.

Record weight, liver and renal function, visual baseline, pregnancy and interactions; rifampicin strongly induces many medicines and doses change with weight.

Completes prolonged CNS sterilisation after the intensive phase.

Continuation TB meningitis regimen

Continue weight-banded rifampicin and isoniazid daily for about 10 further months when drug-susceptible disease is confirmed.

Monitor adherence, liver injury, neuropathy and interactions and obtain specialist advice for interruptions, resistance or paradoxical lesions.

Reduces death and disabling inflammatory complications from basal exudate and oedema.

Dexamethasone adjunct

Give stage-appropriate dexamethasone with a gradual specialist taper over several weeks alongside antituberculous therapy.

Monitor glucose, infection, gastrointestinal and psychiatric effects and account for rifampicin induction; deterioration still requires resistance and hydrocephalus assessment.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Hydrocephalus

Basal inflammatory exudate blocks CSF circulation and causes raised pressure, visual loss, herniation and possible need for neurosurgical shunting.

Stroke and disability

Perforator vasculitis causes cerebral infarction, movement disorder, weakness, language dysfunction and substantial long-term cognitive and functional impairment.

Drug and immune complications

Hepatotoxicity, optic injury, neuropathy, important drug interactions and paradoxical immune reconstitution inflammatory syndrome can interrupt otherwise effective treatment.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review consciousness, cranial nerves, focal deficit, headache and sodium closely during the high-risk early phase.
Track weight, liver and renal function, vision, neuropathy and interactions and adjust all weight-banded drugs after material weight change.
Review mycobacterial culture and susceptibility until final and investigate any missed doses or absorption concern immediately.
Repeat imaging for deterioration and arrange neurorehabilitation, endocrine and public-health follow-up across the full treatment course.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Negative PCR is not exclusion

CSF is paucibacillary and assay sensitivity is incomplete, so the clinical and imaging syndrome can justify immediate treatment.

Find TB outside CSF

Sputum, lymph node or another tissue may yield culture and susceptibility when meningeal samples remain negative.

Deterioration has competing causes

Resistance, non-adherence, hydrocephalus, infarction and paradoxical inflammation can look alike and require simultaneous assessment.

Sodium reveals physiology

Hyponatraemia from SIADH and cerebral salt wasting needs volume-sensitive distinction; reflex fluid restriction can worsen depletion.

11Common pitfallsFrequent interpretation and management errors.

01
Withholding treatment after one negative CSF smear or molecular test despite a convincing basal meningitis syndrome.
02
Using a short pulmonary TB duration for CNS disease without specialist justification.
03
Calling new tuberculomas paradoxical without checking adherence, drug exposure and resistance.
04
Treating hydrocephalus medically while delaying neurosurgical diversion in a deteriorating patient.