Encephalopathy secondary to isoniazid in patients on hemodialysis

Case 1

This 48-year-old-male patient was a known case of end-stage renal failure secondary to diabetic nephropathy and was on regular hemodialysis three times per week for the last 10 months. He was diagnosed as having tuberculosis of the mediastinal lymph node by biopsy 5 months before this presentation. He was treated with rifampicin and INH 300 mg/day in addition to pyrazinamide and ethambutol for first 2 months; pyridoxine 40 mg/day was then added to prevent complications. The patient′s consciousness had deteriorated 3 days before presenting to us; no fever, jaundice, vomiting or headache, and no weakness in any part of the body were observed.

On examination, patient was unconscious with Glasgow Coma Scale of 4, temperature was 36.9°C, blood pressure 126/65 and pulse 70/min, and neck stiffness was negative. Pupils were of normal size and shape, all limbs were flaccid with normal-to-depressed reflexes, planters were down, his chest and hearts in addition to abdomen examination were normal. Therefore, as a differential diagnosis, tuberculous meningitis, encephalitis, and metabolic versus ischemic or toxic encephalopathy were suspected.

His biochemistry and cerebrospinal fluid analysis [Table 1] was unremarkable apart from his renal failure; computed tomography and magnetic radio-imaging of the brain was normal, electroencephalogram showed diffuse theta slow wave all over the brain. Computed tomography of the abdomen and chest was performed to visualize the lymph node and rule out paraneoplastic, which showed mild thickening of the rectosigmoid junction; further, sigmoidoscopy was performed with biopsy, which was normal. Thus, from this presentation and since there was no evidence of neither organic nor metabolic or infectious cause, an INH-induced encephalopathy was suspected (there is no INH level in our laboratory); therefore, INH was stopped and the dose of pyridoxine was increased. After 2 days, the patient could open his eyes and within 7 days he was completely normal and was discharged, with 400 mg/day moxifloxacine as replacement for INH.

Table 1 Hematological investigation and cerebrospinal fluid of both patients

Case 2

This 72-year-old male patient is a known case of end-stage renal failure for the last 2 years secondary to diabetic nephropathy and was on regular hemodialysis three times per week. He was diagnosed as pulmonary tuberculosis 4 months before presentation and started on ethambutol 800 mg every alternate day and pyrazinamide 1200 mg/day for first 2 months, rifampicin 600 mg/day, and INH 300 mg/day with pyridoxine 40 mg/day. He was admitted to the intensive care unit because of deterioration in the level of consciousness 3 days before admission; no other significant history was found.

On examination, the patient was unconscious, could open his eyes to loud voice, with Glasgow Coma Scale of 7, temperature was 37°C; other vital signs were normal, no neck stiffness and other focal neurological sign were recorded, and other system examinations showed unremarkable results. The cerebrospinal fluid analysis was normal; biochemistry test results were normal, apart from renal failure. Also, all septic work up with blood cultures showed negative result. Computed tomography of the brain showed brain atrophy, electroencephalogram showed diffuse slow wave all over the brain. As all septic work up, vascular and organic neurological causes were excluded, an INH toxicity was suspected (there is no INH level in our laboratory); hence, it was stopped and pyridoxine in a dose of 80 mg/day was given through a nasogastric tube. On day 5, the patient was completely conscious and discharged from the intensive care unit on moxifloxacine 400 mg/day as a replacement for INH.