Clinical Case Scenario
A 50-year-old woman with type 2 diabetes mellitus, systemic hypertension, and end-stage kidney disease on maintenance haemodialysis twice weekly presents with progressive drowsiness for 10 days with worsening sensorium, visual hallucinations and confusion for the past 2 days. There is no history of fever, headache, vomiting, seizures, trauma, or recent fall. Her last haemodialysis session was 4 days back.
Two weeks back, she was diagnosed with tuberculous osteomyelitis of the left ankle (subtalar joint) after biopsy demonstrated epithelioid granulomatous inflammation, and GeneXpert MTB/RIF was positive for Mycobacterium tuberculosis. She was started on antitubercular therapy.
Current medications:
On examination, the patient is drowsy, arousable, obeys simple commands but disoriented with intermittent agitation and irrelevant speech. No focal neurological deficits.
Vital signs:
Investigations:
Laboratory Investigations:
ABG: pH 7.45, PaCO₂ 34 mmHg, PaO₂ 102.9 mmHg, HCO₃⁻ 23.4 mmol/L, lactate 0.67 mmol/L
Wrong Answer: ❌ A. Hemodialysis: An ionized calcium of 1.74 mmol/L is significantly elevated and may cause confusion, cognitive dysfunction, weakness, and nausea. While hemodialysis is generally reserved for severe symptomatic or refractory hypercalcaemia, it is justified in this dialysis-dependent patient because she is due for dialysis and low-calcium dialysate can rapidly lower serum calcium while also correcting any uraemic contribution to encephalopathy.
Wrong Answer: ❌ B. Withhold Isoniazid: INH can cause neurotoxicity by inducing functional pyridoxine deficiency, leading to reduced pyridoxal-5-phosphate and impaired GABA synthesis. Patients with chronic kidney disease and haemodialysis are at higher risk. The temporal relationship between starting antitubercular therapy and the onset of symptoms makes INH toxicity a plausible contributor. As the condition is often reversible, withholding INH and giving therapeutic-dose pyridoxine (e.g., 100 mg/day) is appropriate while other causes of encephalopathy are investigated.
Right Answer: ✅ C) Administer Zoledronic acid Zoledronic acid is the least appropriate initial intervention. Bisphosphonates inhibit the osteoclast-induced bone resorption, reducing the calcium level. Although intravenous bisphosphonates are standard therapy in the management of hypercalcaemia, their onset of action is delayed (typically 48–72 hours). More importantly, zoledronic acid is associated with nephrotoxicity and is generally not recommended in patients with severe renal impairment (eGFR <30 mL/min/1.73 m²) or those receiving dialysis. Given the need for rapid symptom control and the availability of safer alternatives in this setting, it is not an appropriate initial choice.
Explanation This patient presenting with encephalopathy has multiple differential diagnoses: 1. Isoniazid neurotoxicity 2. Hypercalcemia 3. PRES 4. CNS Tuberculosis CLINICAL PEARLS 💎 In a dialysis patient with acute encephalopathy and significant hypercalcaemia, think beyond uraemia. • Consider symptomatic hypercalcaemia, isoniazid neurotoxicity, and PRES simultaneously. • Low-calcium haemodialysis and calcitonin are useful initial therapies when rapid calcium reduction is needed. • Zoledronic acid has a delayed onset and is generally not an appropriate initial choice in dialysis-dependent patients. • A normal CT brain does not exclude PRES or CNS tuberculosis; MRI is considerably more sensitive.
Wrong Answer: ❌ D. Administer Calcitonin Calcitonin is faster acting and used when a rapid decrease in calcium levels is needed. The mechanism of action is decreasing osteoclast activity and renal calcium reabsorption, reducing calcium levels. Onset of action is 12 to 24 hours, but it downregulates calcitonin receptors in the bone and kidneys, inducing tachyphylaxis in 48 hours.
Wrong Answer: ❌ E. MRI Brain: MRI Brain is considerably more sensitive for detecting PRES, small infarcts, tuberculomas, meningitis-related changes, and other manifestations of CNS tuberculosis.
