What is the diagnosis and treatment for Central Nervous System (CNS) Tuberculosis (TB)?

Diagnosis and Treatment of CNS Tuberculosis

Diagnosis of CNS Tuberculosis

CNS tuberculosis is a medical emergency requiring immediate empirical treatment when suspected—do not wait for microbiological confirmation, as treatment delay is strongly associated with death. 1

Clinical Presentation and When to Suspect CNS TB

• Suspect CNS TB in patients presenting with subacute onset of headache, fever, altered mental status, focal neurological deficits, or seizures, particularly in high-risk populations (HIV-infected, immunosuppressed, foreign-born from endemic countries, homeless, incarcerated individuals). 2, 1
• The disease has insidious onset and can manifest as tuberculous meningitis (TBM), intracranial tuberculoma, tuberculous abscess, or spinal tuberculosis. 3, 1
• TBM may lead to cranial nerve palsies, hydrocephalus, and infarction due to arteritis of basal perforators. 3

Cerebrospinal Fluid Analysis

• Lumbar puncture with CSF examination is the cornerstone of TBM diagnosis. 1
• Suspect TBM if CSF shows: lymphocytic pleocytosis, elevated protein, and CSF:plasma glucose ratio <50%. 1
• The diagnostic yield of CSF microscopy and culture for Mycobacterium tuberculosis increases with larger CSF volumes submitted; repeat lumbar puncture if diagnosis remains uncertain. 1
• Definitive diagnosis depends on detection of tubercle bacilli in CSF, though this is often delayed or negative. 4

Neuroimaging

• Contrast-enhanced CT or MRI should be performed in all suspected CNS TB cases, preferably within 48 hours of presentation. 4
• MRI offers greater sensitivity and specificity than CT for CNS TB diagnosis. 5
• Imaging is essential for diagnosing cerebral tuberculoma and spinal tuberculosis, though radiological appearances alone do not confirm diagnosis. 1
• Classic imaging findings include basal meningeal enhancement, hydrocephalus, infarcts in basal ganglia distribution, and ring-enhancing lesions (tuberculomas). 3, 6

Microbiological Confirmation

• Attempt tissue diagnosis through histopathology and mycobacterial culture whenever possible, either by biopsy of CNS lesion or diagnostic sampling from extra-neural sites (lung, gastric aspirate, lymph nodes, liver, bone marrow). 1
• Seek extra-neural tuberculosis focus clinically and radiologically in all CNS TB patients, as this may provide safer and more accessible sites for diagnostic sampling. 4
• Culture and drug susceptibility testing should be performed on all specimens to guide therapy. 7, 1

HIV Testing

• All patients with suspected or proven tuberculosis should be offered HIV testing. 1
• HIV infection broadens the differential diagnosis and complicates management, particularly regarding timing of antiretroviral therapy initiation. 7, 1

Treatment of CNS Tuberculosis

Treatment for all forms of CNS tuberculosis should consist of isoniazid, rifampin, pyrazinamide, and ethambutol for 2 months, followed by isoniazid and rifampin for at least 10 months (total 12 months minimum). 1

Standard Treatment Regimen

• Initial phase (2 months): Isoniazid, rifampin, pyrazinamide, and ethambutol daily. 1
• Continuation phase (10 months): Isoniazid and rifampin daily. 1
• This extended 12-month duration for CNS TB differs from the 6-month regimen used for pulmonary TB due to uncertain CNS drug penetration, disease severity, and risk of undetected drug resistance. 7, 4

Adjunctive Corticosteroids

• All patients with tuberculous meningitis should receive adjunctive corticosteroids (dexamethasone or prednisolone) at presentation, regardless of disease severity. 1
• Corticosteroids are beneficial in preventing cardiac constriction from tuberculous pericarditis and decreasing neurological sequelae of TBM, especially when administered early. 7
• This recommendation applies even to HIV-infected patients with TBM. 1, 4

Directly Observed Therapy

• Directly observed therapy (DOT) should be implemented for all TB patients to ensure compliance and prevent drug-resistant TB. 2
• A case manager should be assigned to each patient to ensure adequate education, continuous standard therapy, and contact evaluation. 2

Monitoring During Treatment

• Clinical monitoring should occur at least monthly, assessing for signs of hepatotoxicity (nausea, vomiting, abdominal pain, jaundice, dark urine). 7
• Baseline laboratory testing is indicated for HIV-infected persons, pregnant women, those in immediate postpartum period, persons with liver disease history, regular alcohol users, and those at risk for chronic liver disease. 7
• Routine laboratory monitoring during treatment is indicated only for patients with abnormal baseline tests and persons at risk for hepatic disease. 7

Special Considerations

HIV-Infected Patients

• For HIV-infected patients with CNS TB and CD4 counts <50 cells/μL, antiretroviral therapy (ART) should be started within 2 weeks of initiating TB treatment for non-CNS TB, but delayed by 8 weeks for CNS TB due to higher risk of immune reconstitution inflammatory syndrome (IRIS). 7
• The optimal timing for ART initiation in MDR-TB of the CNS remains uncertain; close clinical monitoring is warranted. 7
• Drug interactions between antiretroviral and anti-TB agents must be carefully managed, particularly with rifamycins. 7

Drug-Resistant CNS TB

• Drug resistance is strongly associated with previous TB treatment. 4
• Never add a single drug to a failing regimen—treatment must include at least 2 new agents to which the organism is susceptible. 4
• Consultation with a TB expert is recommended for all drug-resistant cases. 8

Hydrocephalus Management

• Early ventriculoperitoneal shunting should be considered in patients with hydrocephalus failing medical management. 4

Pediatric Patients

• Children with CNS TB should be managed by a pediatrician with expertise in pediatric tuberculosis or with input from a pediatric infectious diseases unit. 1
• Ethambutol dosing requires careful monitoring in children whose visual acuity cannot be assessed. 8

Critical Pitfalls to Avoid

• Do not delay empirical treatment while awaiting microbiological confirmation—the single most important determinant of outcome is the stage at which treatment is started. 1, 4
• Do not use tuberculin skin test or IGRA to diagnose active TB disease; these tests are for latent TB infection only. 2, 9
• Do not treat CNS TB with the standard 6-month pulmonary TB regimen; minimum 12 months is required. 1, 4
• Do not start ART too early in HIV-infected patients with CNS TB (wait 8 weeks) due to IRIS risk. 7
• Do not exclude CNS TB based on negative CSF smear or culture alone; clinical and radiographic findings must guide empirical treatment decisions. 1