Paediatrics chapters
Tuberculous meningitis
The most serious form of childhood tuberculosis: how it arises from primary infection, its three clinical stages, the typical CSF and scan findings, and the long drug and steroid treatment.
- TBM is a secondary complication of primary tuberculosis, commonest under 5 years and within 6 months of primary infection; caseous Rich foci burst into the CSF and a thick basal exudate traps cranial nerves (III, VI, VII) and blocks CSF flow (communicating hydrocephalus).
- The onset is insidious in three stages of about a week each: vague illness, then meningeal signs, cranial nerve palsies and raised ICP, then coma, decerebrate rigidity and fixed pupils.
- CSF: raised pressure, lymphocytes, very high protein, low glucose, cobweb clot; treat with four drugs for about 12 months plus steroids; outcome depends on the stage at which treatment starts.
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Overview
Tuberculous meningitis (TBM) is inflammation of the pia-arachnoid by Mycobacterium tuberculosis. It is the most serious complication of childhood tuberculosis, complicating about 1 in 300 untreated primary infections. It is still common in Pakistan, where tuberculosis is endemic, and its outcome depends almost entirely on how early treatment starts.
Epidemiology
- Highest incidence under 5 years; the risk is greatest within 6 months of the primary infection.
- Not reported under 4 months, because the disease process needs at least that long to develop.
- It is always secondary; the primary focus is usually in the lungs.
- A history of contact with an adult with tuberculosis is common; measles may precede it.
Pathogenesis
- During the silent lymph-blood spread of primary infection, bacilli seed the cortex, meninges and choroid plexus and form small caseous foci (Rich foci).
- A focus enlarges and discharges bacilli into the subarachnoid space.
- A thick gelatinous exudate collects at the base of the brain, around the brainstem:
- It traps the 3rd, 6th and 7th cranial nerves.
- It inflames and blocks arteries (vasculitis, infarcts).
- It obstructs the basal cisterns, causing communicating hydrocephalus.
- Inflammation also causes cerebral oedema.
The three lesions behind most TBM signs are basal exudate, hydrocephalus and vasculitis with infarction.
Clinical features
The onset is usually gradual over weeks, but it can be rapid in young infants, who may develop hydrocephalus, infarcts or seizures within days. Akbar divides the illness into three stages, each lasting roughly a week, with overlap.
| Stage | Main features |
|---|---|
| Stage 1: prodrome (1-2 weeks) | Non-specific: listless, irritable, loses interest in play, low-grade fever, anorexia, vomiting, constipation, weight loss, headache, drowsiness; no focal signs; loss or arrest of milestones in infants |
| Stage 2: meningeal irritation and raised ICP | Neck stiffness, Kernig and Brudzinski signs, brisk reflexes and extensor plantars; severe persistent (often occipital) headache; cranial nerve palsies: sixth (squint), third, seventh; confusion; bulging fontanelle and separated sutures ("cracked pot" note) in infants, papilloedema in older children; choroid tubercles; seizures |
| Stage 3: coma | Coma, high irregular fever, hemiplegia or paraplegia, opisthotonus, decerebrate rigidity, dilated fixed pupils, failing vital signs; death if untreated |
- Tache cérébrale: stroking the skin leaves a raised red line within 30-60 seconds that lasts minutes; sometimes seen.
- Nelson describes the same course: low fever, headache and subtle personality change, then basilar meningitis with cranial nerve involvement, raised ICP, declining mental state and coma.
A child with a few weeks of irritability, vomiting and fever who then develops a squint is TBM until proved otherwise. Pyogenic meningitis is much more abrupt.
Investigations
CSF
| Feature | Typical finding |
|---|---|
| Pressure | Raised |
| Appearance | Clear, hazy or straw-coloured; a cobweb (pellicle) clot forms on standing |
| Cells | 10-500/mm³, lymphocytes (neutrophils may predominate very early) |
| Protein | Markedly raised; extremely high with spinal block or hydrocephalus |
| Glucose | Low (usually under 40 mg/dl), but rarely as low as in pyogenic meningitis |
| Organisms | Ziehl-Neelsen stain may show acid-fast bacilli (often negative); culture is the standard; PCR helps confirm |
Other tests
- Tuberculin (Mantoux) test: negative in about half, so a negative test does not exclude TBM. Nelson notes an interferon-gamma release assay (IGRA) as an alternative in older children.
- Chest X-ray: often shows hilar nodes, pneumonia or miliary shadows, but can be normal in a sizeable minority.
- ESR high; blood count usually normal with lymphocytes.
- Gastric lavage (early-morning swallowed sputum) for bacilli; lymph node biopsy if present.
- Fundoscopy: choroid tubercles, papilloedema, optic atrophy.
- CT or MRI: basilar (basal) enhancement, communicating hydrocephalus, infarcts, oedema and tuberculomas. The scan may be normal early.
A CSF lymphocytosis with very high protein and low glucose, plus basal enhancement and hydrocephalus on CT, is the classic TBM picture.
TBM compared with other meningitis
| Feature | Tuberculous | Pyogenic | Viral |
|---|---|---|---|
| Onset | Weeks | Hours to 2-3 days | Days |
| Cells | Lymphocytes, 10-500 | Neutrophils, often thousands | Lymphocytes, usually few hundred |
| Protein | Very high | High | Normal or mildly raised |
| Glucose | Low | Very low | Normal |
| Special | Cobweb clot, AFB | Gram stain organism | PCR for virus |
Management
Most children are admitted at the start and complete the long course as outpatients. Follow the current national tuberculosis programme guideline for regimens, because they are updated.
Antituberculous drugs
Akbar recommends starting four drugs and continuing treatment for 12 months; Nelson gives 2 months of isoniazid, rifampicin, pyrazinamide and a fourth drug (an aminoglycoside or ethionamide), then 7-10 months of isoniazid and rifampicin, 9-12 months in total.
| Drug | Dose (Akbar) | Key points |
|---|---|---|
| Isoniazid | 10-15 mg/kg/day | First-choice drug; enters CSF well; hepatotoxicity, peripheral neuropathy (pyridoxine antagonism), optic neuritis |
| Rifampicin | 10-20 mg/kg/day, before breakfast | Good CSF entry; orange urine and tears, hepatotoxicity (more with isoniazid) |
| Pyrazinamide | 30 mg/kg/day for the first 2-3 months | Enters CSF readily; arthralgia, hyperuricaemia |
| Streptomycin | Intramuscular for the first 2 months | Enters CSF only through inflamed meninges; ototoxic and nephrotoxic |
| Ethambutol | 15-25 mg/kg once daily | Optic neuritis; Akbar advises against it under 6 years because vision cannot be tested |
- Mild rises in liver enzymes (up to three times normal) can occur at 6-12 weeks; treatment continues unless the child becomes ill.
- Pyridoxine (Akbar: 10 mg daily) is given to children with poor diets and breastfed infants to prevent neuropathy.
Corticosteroids
- Prednisolone 1-2 mg/kg/day, continued for about 6-8 weeks and then tapered; dexamethasone IV if the child cannot swallow.
- Steroids reduce death and long-term neurological damage by lessening vasculitis, inflammation, oedema, raised ICP and adhesions.
Supportive care
- Monitor vital signs, conscious level, raised ICP and SIADH daily.
- Anticonvulsants (phenobarbitone) for seizures; paracetamol and sponging for fever.
- Nasogastric feeding with enough calories and protein; correct malnutrition.
- Comatose care: turn every 2 hours, bladder, bowel, eyes and mouth.
- Hydrocephalus may need a ventriculoperitoneal shunt.
- Screen the family for tuberculosis and treat infected members.
Do not wait for a positive smear or culture. Start treatment on clinical and CSF suspicion, because delay moves the child into a worse stage.
Ethambutol is avoided in young children because optic neuritis cannot be monitored; streptomycin is ototoxic.
Complications and sequelae
- Hydrocephalus.
- Cranial nerve palsies (3rd, 6th, 7th), blindness from optic atrophy, deafness (disease or streptomycin).
- Hemiplegia, paraplegia or monoplegia from infarcts.
- Epilepsy, intellectual disability, behaviour problems.
- Endocrine problems such as diabetes insipidus from hypothalamic damage.
- Tuberculoma.
Prognosis
- Untreated TBM is almost always fatal.
- Outcome depends on the age of the child and above all the stage when treatment starts: near-complete recovery is expected in stage 1, while in stage 3 many die and most survivors have lasting deficits.
- Infants and young children do worse than older children.
- Nelson notes most childhood TBM occurs in developing countries, where the outlook is poor because diagnosis is late.
"Stage decides the fate": the earlier the stage at diagnosis, the better the outcome.
Prevention
- BCG at birth protects young children mainly against miliary disease and TBM (follow the current national immunisation schedule).
- Contact tracing and treatment of latent infection in children exposed to an infectious adult.
Expect: TBM as a complication of primary infection within 6 months, under 5 years; Rich focus; basal exudate with 3rd, 6th and 7th nerve palsies and communicating hydrocephalus; three clinical stages; CSF with lymphocytes, very high protein, low glucose and cobweb clot; negative tuberculin test in half; CT basal enhancement and hydrocephalus; four-drug treatment for about 12 months with steroids; stage at diagnosis as the main prognostic factor; ethambutol caution in young children.
Quick revision
- Secondary to primary TB; 1 in 300 primary infections; under 5; within 6 months.
- Rich focus ruptures; basal exudate; vasculitis; communicating hydrocephalus.
- Stage 1 vague; stage 2 meningism, cranial palsies, raised ICP; stage 3 coma, decerebrate rigidity.
- CSF: lymphocytes 10-500, protein very high, glucose low, cobweb.
- Mantoux negative in half; chest X-ray may be normal.
- CT: basal enhancement, hydrocephalus, infarcts, tuberculoma.
- Four drugs, 9-12 months; steroids 6-8 weeks; pyridoxine.
- Prognosis set by the stage at the start of treatment.
Written by The House Job from standard references (Basis of Paediatrics by Pervez Akbar; Nelson Essentials of Paediatrics).
FAQ
Why does tuberculous meningitis cause cranial nerve palsies?
The thick exudate collects at the base of the brain where the cranial nerves leave the brainstem, trapping the third, sixth and seventh nerves in particular.
Does a negative Mantoux test rule out TBM?
No. It is negative in about half of children with TBM, especially the very ill or malnourished, so diagnosis rests on the history, CSF and scan.
Why are steroids given in TBM?
They reduce vasculitis, brain swelling, raised pressure and adhesions, and lower both death and long-term neurological damage when added to the antituberculous drugs.
How long is treatment?
Akbar advises 12 months of treatment starting with four drugs; Nelson gives 9-12 months, with four drugs for the first 2 months then isoniazid and rifampicin.