What's the approach to a patient with a history of pulmonary TB, recently diagnosed with TB lymphadenitis, on anti-tubercular therapy (AKT), presenting with altered sensorium?

Approach to a 70-Year-Old Male with TB Lymphadenitis on AKT Presenting with Altered Sensorium

This patient requires immediate evaluation for tuberculous meningitis (TBM), which is the most critical diagnosis to exclude given the combination of active TB treatment and new-onset altered sensorium. 1

Immediate Diagnostic Workup

Neurological Assessment

• Perform urgent lumbar puncture unless contraindicated by signs of raised intracranial pressure (papilledema, focal neurological deficits, or imaging evidence of mass effect). 1
• CSF analysis should include: cell count with differential, protein, glucose (with simultaneous serum glucose), AFB smear, mycobacterial culture, and if available, GeneXpert MTB/RIF or other molecular testing. 1
• Obtain brain imaging (CT or preferably MRI) before LP if any concern for space-occupying lesion or raised intracranial pressure. 1

Alternative Diagnoses to Consider

• Drug-induced hepatotoxicity with hepatic encephalopathy: Check liver function tests (AST, ALT, bilirubin, INR, albumin) immediately, as isoniazid, rifampin, and pyrazinamide can all cause hepatitis. 1
• Paradoxical reaction: New or worsening neurological symptoms can occur despite appropriate therapy, particularly in the first 2-3 months of treatment. 1
• Electrolyte disturbances or hypoglycemia: Check basic metabolic panel and glucose. 2
• Drug resistance with disseminated TB: Consider if patient was inadequately treated during first TB episode or has risk factors for MDR-TB. 1

Management Based on Findings

If TBM is Confirmed or Highly Suspected

• Extend treatment duration to 9-12 months (not the standard 6 months used for lymph node TB). 1
• Add corticosteroids immediately: Dexamethasone or prednisolone is recommended for all patients with tuberculous meningitis to reduce mortality and severe disability. 1
• Continue four-drug regimen (isoniazid, rifampin, pyrazinamide, ethambutol) with careful monitoring. 1
• Do not reduce to two-drug continuation phase as you would with pulmonary TB; maintain intensive therapy longer. 1

If Drug-Induced Hepatotoxicity is Present

• Stop all hepatotoxic drugs immediately if ALT >5x upper limit of normal with symptoms, or >3x with jaundice. 1
• Once liver enzymes normalize, reintroduce drugs sequentially starting with rifampin (least hepatotoxic), then isoniazid, then pyrazinamide (most hepatotoxic). 1
• Consider alternative regimen with fluoroquinolone (levofloxacin or moxifloxacin) plus ethambutol and an injectable agent if unable to tolerate standard drugs. 1, 3

If Paradoxical Reaction is Suspected

• Continue anti-TB therapy unchanged as this represents an immune reconstitution phenomenon, not treatment failure. 1
• Consider corticosteroids (prednisone 1-2 mg/kg/day) for severe paradoxical reactions with significant clinical impact. 1
• Monitor closely with serial clinical assessments and imaging. 1

If Drug Resistance is Suspected

• Send sputum or other available specimens for drug susceptibility testing including both first-line and second-line drugs. 1
• Do not add a single drug to the current regimen—this is a critical error that leads to further resistance. 1
• If patient is critically ill, start empirical expanded regimen with at least three drugs the organism is likely susceptible to: a fluoroquinolone (levofloxacin or moxifloxacin), an injectable agent (amikacin, kanamycin, or capreomycin), and an oral agent (linezolid, cycloserine, or ethionamide). 1
• Consult a TB specialist immediately for management of suspected drug-resistant TB. 1

Critical Monitoring Parameters

During Initial Evaluation

• Assess for signs of increased intracranial pressure: headache, vomiting, altered consciousness, focal deficits. 1
• Check renal function as ethambutol dosing requires adjustment in renal insufficiency, and the patient's age puts him at risk. 1
• Review medication adherence history: Non-adherence is the most common cause of treatment failure and acquired resistance. 1

Ongoing Management

• Monthly clinical evaluations to assess treatment response, adherence, and adverse effects. 2
• Repeat liver function tests at baseline, 2 weeks, monthly, and any time symptoms suggest hepatotoxicity (nausea, vomiting, abdominal pain, jaundice). 1, 2
• Serial neurological assessments if TBM is diagnosed, as clinical deterioration can occur despite appropriate therapy. 1

Common Pitfalls to Avoid

• Do not assume altered sensorium is simply a side effect of medications—TBM is life-threatening and requires immediate diagnosis and extended treatment. 1
• Do not continue standard 6-month therapy if TBM is diagnosed—this is inadequate and associated with poor outcomes. 1
• Do not delay corticosteroids if TBM is confirmed—they significantly reduce mortality and morbidity. 1
• Do not attribute all neurological symptoms to paradoxical reaction without first excluding TBM, hepatic encephalopathy, and other metabolic causes. 1
• Do not restart all hepatotoxic drugs simultaneously if drug-induced liver injury occurred—sequential reintroduction is essential. 1