What is the approach to a patient with pulmonary tuberculosis on antitubercular treatment (ATT) who presents with a seizure?

Approach to Seizure in a Pulmonary TB Patient on Anti-Tubercular Treatment

Immediately stabilize the seizure with standard anticonvulsants, then administer intravenous pyridoxine (vitamin B6) 100-200 mg, as isoniazid-induced seizures are often refractory to conventional anticonvulsants alone. 1

Immediate Management

Acute Seizure Control

• Administer pyridoxine (vitamin B6) 100-200 mg IV immediately while managing the seizure with standard anticonvulsants, as isoniazid can cause seizures even at therapeutic doses by depleting vitamin B6 1, 2
• Seizures from isoniazid toxicity are characteristically refractory to standard anticonvulsants but respond to pyridoxine 3, 2
• Standard seizure management protocols apply: secure airway, obtain IV access, give benzodiazepines, but recognize these may be insufficient without pyridoxine 2

Critical Diagnostic Evaluation

Determine if this is CNS tuberculosis versus drug-induced seizure - this distinction is life-threatening and changes management completely:

• Perform urgent lumbar puncture to evaluate for tuberculous meningitis (TBM): look for lymphocytic pleocytosis, elevated protein, and CSF:plasma glucose <50% 4
• Obtain urgent brain imaging (CT or MRI) to identify tuberculomas or other structural lesions 4, 5
• Check serum sodium urgently - tuberculosis can cause SIADH leading to hyponatremia and seizures 6
• Measure serum vitamin B6 levels if available, though treatment should not be delayed waiting for results 2

Differential Diagnosis Framework

Drug-Induced Seizures (Most Common in Pulmonary TB)

• Isoniazid toxicity causes seizures through pyridoxine depletion, even at standard therapeutic doses of 600 mg 3, 2
• Cycloserine (if being used for drug-resistant TB) causes seizures in up to 16% at doses >500 mg/day 1
• Ethionamide can cause neurotoxicity including seizures 1
• Fluoroquinolones (ciprofloxacin) can cause seizures 1

CNS Tuberculosis

• Tuberculous meningitis is a medical emergency requiring immediate empirical treatment - do not wait for confirmation 4
• Tuberculomas can present with seizures without meningitis 4, 5
• Early seizures relate to meningeal irritation and cerebral edema; late seizures indicate structural lesions 5

Metabolic Causes

• SIADH-induced hyponatremia from tuberculosis itself can cause status epilepticus, even with mild pulmonary involvement 6

Treatment Algorithm

If Drug-Induced Seizure is Suspected:

1. Continue pyridoxine supplementation at 100-200 mg/day prophylactically going forward 1
2. Review the ATT regimen: identify if cycloserine, ethionamide, or fluoroquinolones are being used 1
3. If on cycloserine: reduce dose to ≤500 mg/day or discontinue if seizures persist; measure serum levels targeting 20-35 mg/mL 1
4. Continue first-line TB drugs (isoniazid, rifampicin, pyrazinamide, ethambutol) with pyridoxine supplementation 4

If CNS Tuberculosis is Confirmed or Highly Suspected:

1. Start empirical 4-drug anti-TB therapy immediately (isoniazid, rifampicin, pyrazinamide, ethambutol) for 2 months, then 2 drugs (isoniazid, rifampicin) for at least 10 months 4
2. Add adjunctive corticosteroids (dexamethasone or prednisolone) for all TBM patients regardless of severity 4
3. Initiate antiseizure medications and continue until infection is controlled 5
4. Increase CSF sampling volume and repeat lumbar puncture if diagnosis remains uncertain, as diagnostic yield increases with volume 4

If Hyponatremia from SIADH:

• Correct sodium cautiously while treating underlying tuberculosis 6
• Recognize that SIADH can occur even with mild pulmonary TB 6

Critical Monitoring

• Neuropsychiatric assessment at least monthly for patients on cycloserine or ethionamide 1
• Monitor phenytoin levels if using both phenytoin and isoniazid, as isoniazid increases phenytoin levels requiring dose adjustment 1
• Serial imaging if tuberculoma suspected, as structural lesions increase epilepsy risk 5

Key Pitfalls to Avoid

• Never delay empirical TBM treatment waiting for microbiological confirmation - treatment delay is strongly associated with death 4
• Do not assume seizures are only from drug toxicity without ruling out CNS TB - this is a fatal mistake 4, 5
• Do not stop first-line TB drugs for minor side effects; use pyridoxine supplementation instead 1, 7
• Do not use single-drug formulations initially if hepatotoxicity is a concern; establish safety first 1
• Young age, refractory seizures, tuberculomas, and cortical involvement increase epilepsy risk - these patients need prolonged antiseizure treatment 5