What is the cause of sudden decline in level of consciousness in a patient with a tuberculoma (tuberculous brain tumor) after starting Antitubercular Therapy (ATT)?

From the Guidelines

A sudden decline in level of consciousness in a patient with a tuberculoma after starting Antitubercular Therapy (ATT) is most likely due to a paradoxical reaction, which requires immediate management with corticosteroids. This reaction, as described by the American Thoracic Society 1, occurs when patients experience a temporary exacerbation of symptoms, signs, or radiographic manifestations of tuberculosis after beginning antituberculosis treatment. The cause of this reaction is thought to be the reconstitution of immune responsiveness brought about by antituberculosis therapy, leading to an excessive immune response to mycobacterial antigens released when treatment kills the bacteria.

Key features of a paradoxical reaction include:

• High fevers
• Increase in size and inflammation of involved lymph nodes
• New lymphadenopathy
• Expanding central nervous system lesions
• Worsening of pulmonary parenchymal infiltrations
• Increasing pleural effusions These findings should be attributed to a paradoxical reaction only after a thorough evaluation has excluded other possible causes, especially tuberculosis treatment failure, as noted in the guidelines 1.

In the context of a tuberculoma, the paradoxical reaction can cause increased edema around the tumor, worsening mass effect and neurological symptoms. Other possible causes to consider include drug toxicity (particularly isoniazid-induced encephalopathy), electrolyte disturbances, or development of hydrocephalus. The patient should undergo urgent neuroimaging to assess for increased edema or hydrocephalus, and liver function tests and electrolytes should be checked to rule out drug toxicity.

Despite this reaction, it is crucial to continue the full ATT regimen (typically isoniazid, rifampin, pyrazinamide, and ethambutol) unless there is evidence of drug toxicity, as interrupting treatment can lead to treatment failure and drug resistance. Management with corticosteroids, such as dexamethasone, should be initiated to reduce inflammation and edema, with a typical dose of 0.4 mg/kg/day (typically 16-24 mg daily for adults) in divided doses, then tapered over 6-8 weeks while continuing the ATT regimen.

From the Research

Causes of Sudden Decline in Level of Consciousness

• A sudden decline in level of consciousness in a patient with a tuberculoma after starting Antitubercular Therapy (ATT) can be attributed to several factors, including paradoxical reactions (PRs) 2, 3.
• Paradoxical reactions are a known complication of anti-tuberculosis therapy, where new lesions or worsening of existing lesions occur after the initiation of treatment 2.
• These reactions can manifest as an increase in size or number of tuberculomas, leading to increased intracranial pressure and subsequent decline in level of consciousness 3, 4.
• Another possible cause is the immune reconstitution inflammatory syndrome (IRIS), which can occur in response to the restoration of the immune system after starting ATT 3, 5.

Diagnostic and Treatment Challenges

• The diagnosis of paradoxical reactions or IRIS can be challenging, and a high index of suspicion is required, especially in patients with a history of tuberculous meningitis or cerebral tuberculoma 2, 3.
• Imaging studies such as MRI or CT scans can help identify new or worsening lesions, but may not always distinguish between paradoxical reactions and treatment failure 3, 4.
• The use of adjunctive corticosteroid therapy may be beneficial in managing paradoxical reactions and IRIS, but the optimal duration and dosage of corticosteroids are not well established 2, 6.