What is the mortality rate of Central Nervous System (CNS) tuberculosis?

From the Guidelines

Central nervous system (CNS) tuberculosis has a high mortality rate, ranging from 20-50% despite appropriate treatment, with the highest mortality rates seen in tuberculous meningitis, especially in patients with advanced disease or HIV co-infection. The mortality rate can increase to 60% in patients with advanced disease or HIV co-infection 1. Factors associated with poor outcomes include delayed diagnosis, advanced stage at presentation (altered consciousness, neurological deficits), HIV co-infection, drug resistance, and young age (especially children under 5) 1.

Early initiation of anti-tuberculosis therapy significantly improves survival, with the standard treatment regimen including isoniazid (5-10 mg/kg/day), rifampin (10 mg/kg/day), pyrazinamide (15-30 mg/kg/day), and ethambutol (15-20 mg/kg/day) for 2 months, followed by isoniazid and rifampin for an additional 7-10 months 1.

• Adjunctive corticosteroids (dexamethasone or prednisolone) reduce mortality by decreasing inflammation and intracranial pressure, and are recommended for patients with tuberculous meningitis, especially those with a decreased level of consciousness 1.
• The high mortality is due to the pathophysiology of CNS TB, which causes intense inflammation leading to vasculitis, infarction, hydrocephalus, and raised intracranial pressure.
• Prompt diagnosis using CSF analysis, neuroimaging, and molecular tests like GeneXpert MTB/RIF, followed by immediate treatment initiation, is crucial for improving survival outcomes 1.

The use of adjunctive corticosteroid therapy with dexamethasone or prednisolone tapered over 6–8 weeks is recommended for patients with tuberculous meningitis, as it has been shown to reduce mortality 1. It is essential to note that the optimal approach for initiation of antiretroviral therapy (ART) in patients with CNS TB and HIV remains uncertain, and close clinical monitoring is warranted 1.

From the Research

Mortality of CNS Tuberculosis

• The mortality rate of CNS tuberculosis is high if left untreated, with death occurring within five to eight weeks of onset 2.
• Vasculitis leading to infarcts in the basal ganglia is a major determinant of morbidity and mortality in CNS tuberculosis 2.
• Treatment delay is strongly associated with death, and empirical anti-tuberculosis therapy should be started promptly in all patients in whom the diagnosis of CNS tuberculosis is suspected 3.
• Adjunctive corticosteroid therapy has been shown to reduce morbidity and mortality in all but late-stage disease 2, 3.

Factors Affecting Mortality

• The use of antituberculosis drugs can have neurological manifestations and toxicities, which can affect mortality 4.
• Isoniazid, rifampicin, and pyrazinamide are the most commonly used antituberculosis drugs, and their pharmacokinetics and safety/tolerability can impact mortality 5.
• Higher rifampicin doses may be warranted in the treatment of children and adolescents with CNS tuberculosis to improve outcomes 5.
• The development of drug-induced liver injury (DILI) is a concern in the treatment of CNS tuberculosis, and higher plasma concentrations of isoniazid, rifampicin, and pyrazinamide may be associated with an increased risk of DILI 5.

Treatment Outcomes

• Early treatment initiation and the use of adjunctive corticosteroid therapy can improve outcomes in CNS tuberculosis 2, 3.
• The combination of meningeal enhancement and any degree of hydrocephalus on brain CT and MRI is strongly suggestive of CNS tuberculosis, and can aid in diagnosis and monitoring of the clinical course 2.
• Treatment regimens that include isoniazid, rifampicin, pyrazinamide, and ethambutol can be effective in reducing morbidity and mortality in CNS tuberculosis 2, 3, 6.