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CNS TUBERCULOSIS (Neurological Tuberculosis)

Sharma & Mohan – Textbook of Tuberculosis and Nontuberculous Mycobacterial Diseases, Chapter 17

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CLASSIFICATION

1. TB Meningitis (TBM) – accounts for 70–80% of all neurological TB
2. Intracranial Tuberculoma
3. TB Radiculomyelitis (TBRM)

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I. TUBERCULOSIS MENINGITIS (TBM)

Epidemiology

• Highest incidence in first 3 years of life in developing countries
• 5–10% of patients with active pulmonary TB develop neurological TB
• Risk 5× higher in HIV-seropositive individuals
• Average symptom duration before diagnosis: 11–72 days

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Pathogenesis

• Caused by Mycobacterium tuberculosis (rarely bovine/avian/NTM)
• TBM is always secondary to TB elsewhere in the body
• Critical event: rupture of a subependymally located Rich focus → infectious material discharged into subarachnoid space
• Predisposing factors: intercurrent viral infections, advanced age, malnutrition, alcoholism, HIV/AIDS, corticosteroids, immunosuppressants

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Pathology

TB Encephalopathy (paediatric): diffuse brain oedema, perivascular myelinolysis, haemorrhagic leucoencephalitis with little meningitis — a hypersensitivity reaction to tuberculoproteins.

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Clinical Features

• Prodromal phase (2–3 weeks): vague ill-health, apathy, irritability, anorexia, behavioural changes
• Meningitic phase: fever, headache, vomiting, neck stiffness
• Focal signs: convulsions (20–30%), cranial nerve palsies (20–30%; CN VI most common), hemiparesis
• Visual loss: 4–35% (opticochiasmatic arachnoiditis, arteritis, hydrocephalus, ethambutol toxicity)
• Terminal (untreated): deep coma, decerebrate/decorticate posturing; death in 5–8 weeks

Clinical Staging (MRC System)

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Diagnosis

Imaging

• CT/MRI: basal meningeal enhancement (60%), hydrocephalus (50–80%), cerebral infarction (28%), tuberculomas (10%), gyral enhancement
• Common sites of exudate: basal cisterna ambiens, suprasellar cistern, Sylvian fissures
• Gadolinium MRI superior to CT for: basal meningeal enhancement, small tuberculomas, focal basal ganglia infarcts, brainstem lesions

Tuberculin Skin Test (TST)

• Positive in 40–65% adults; 85–90% children (western data)
• Low specificity in developing countries (BCG, environmental mycobacteria)

CSF Analysis

Classical CSF pattern in 66.8%; pseudopyogenic in 14.5%; normal in 5% (Thomas et al.)

Molecular Methods

• PCR (IS6110 primers): nested amplification → 90.5% sensitivity (Liu et al.)
• Xpert MTB/RIF (CBNAAT): pooled sensitivity 80.5%, specificity 97.8% (INDEX-TB); used as adjunctive test; negative result does NOT exclude TBM

Immunological/Biochemical Tests

• ADA (adenosine deaminase): elevated in 60–100% (false positives in other meningitides)
• ELISA: antibodies against glycolipids, LAM, A-60 antigen; sensitivity 61–90%, specificity 58–100%
• Tuberculostearic acid (TSA): sensitivity ~75%, specificity 96%
• Circulating immune complexes: antigen + antibody assay together → 82% detection

Differential Diagnosis of TBM

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Treatment

Anti-TB Regimen

• 4-drug intensive phase (2 months): Isoniazid (H) + Rifampicin (R) + Pyrazinamide (Z) + Ethambutol (E) or Streptomycin (S)
• Continuation phase: RHE continued
• Pyridoxine (10–100 mg/day) to prevent INH-induced peripheral neuropathy

Duration

• INDEX-TB Guidelines: minimum 9 months (standard first-line treatment)
• BTS/ATS/CDC/IDSA: 12 months for uncomplicated TBM
• Evidence supports 6–12 months as adequate; 18–24 months no longer routinely recommended

Corticosteroids

• Clinical stages 2 and above
• Raised ICP
• Focal neurological deficits (arteritis)
• Cerebral/perilesional oedema, hydrocephalus, infarcts, opticochiasmatic pachymeningitis

Thwaites et al. (n=545, Vietnam): dexamethasone reduced death (p=0.01) but did not significantly reduce severe disability. INDEX-TB: corticosteroids strongly recommended in HIV-seronegative TBM.

HIV-Associated TBM

• Anti-TB + ART + cotrimoxazole prophylaxis
• ART: start as soon as TB treatment tolerated, not later than 8 weeks of anti-TB treatment (WHO)

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Complications & Sequelae

Hydrocephalus Management

• Stages I–II (communicating): furosemide, acetazolamide, steroids, serial LP
• Stages III–IV (altered sensorium): CSF diversion — EVD, VP shunt, endoscopic third ventriculostomy (ETV preferred); Ommaya reservoir if EVD >4–5 days

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Prognosis & Poor Outcome Factors

• Stage 1 treatment → cure rate 85–90%
• Stage 3–4 → mortality 78–79%
• Poor prognostic factors: advanced clinical stage, delayed diagnosis, extremes of age (<3 years, >50 years), MDR-TB, HIV (CD4 <0.2×10⁹/L), hydrocephalus, raised ICP, vasculitis, hyponatraemia, high CSF protein (>2 g/L), seizures, no BCG vaccination

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II. INTRACRANIAL TUBERCULOMA

Definition & Pathology

• Mass of granulation tissue — conglomeration of microscopic tubercles
• Central caseous necrosis → fibrous encapsulation → may liquefy to form TB abscess
• Size: few mm to 3–4 cm
• <20 years: usually infratentorial; adults: supratentorial
• Epidemiology: constitutes 5–10% of intracranial SOLs in developing world

Diagnosis

• CT/MRI: nodular enhancing lesion with central hypointensity; ring/homogeneous/patchy enhancement
• MR Spectroscopy: lipid peak at 1.2 ppm (characteristic)
• MRI types:

Management

• Medical (first-line): Anti-TB therapy — lesions begin to decrease within 2 months
• Corticosteroids for cerebral oedema
• Surgery: large lesions with midline shift, severe ICP, expanding during treatment, suspicion of alternate diagnosis (glioma/metastasis)
• Paradoxical expansion during treatment — immunological (IRIS-like); managed with steroids

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III. TB ABSCESS

• Rare; usually immunosuppressed patients
• Encapsulated pus containing viable TB bacilli without classic TB granuloma
• Differentiation from tuberculoma: diffusion-weighted MRI shows diffusion restriction (favours abscess)
• MR spectroscopy: lipid-lactate peak (absent succinate/acetate distinguishes from pyogenic)
• Treatment: surgical aspiration/excision + anti-TB drugs

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IV. TB RADICULOMYELITIS (TBRM)

Pathogenesis

• Primary TB lesion, OR downward extension of TBM, OR secondary extension from vertebral TB

Pathology & Clinical Features

• Extensive tenacious exudates encasing spinal cord, impinging on roots
• Subacute-to-chronic progressive flaccid paraparesis + positive Babinski, root pains, paraesthesias, bladder disturbance
• Lumbosacral most common site; cervical also affected

Investigations

• CSF: lymphocytic pleocytosis, hypoglycorrhachia, very high protein (CSF flow block)
• Imaging: Gadolinium-enhanced MRI preferred; findings — loculation/obliteration of spinal subarachnoid space, matting of nerve roots, meningeal enhancement, syringomyelic cavity (late complication)

Management

• Anti-TB treatment + corticosteroids (vasculitis of spinal vessels)
• Decompressive surgery: very limited role; often fails to arrest progression

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SUMMARY TABLE: CSF in Various Meningitides

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