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Fatal toxic encephalopathy in a uraemic patient: case report A 59-year-old haemodialysis-dependent woman with uraemia developed toxic encephalopathy with progressive movement disorders and mental changes while receiving amantadine and pramipexole for Parkinsonian tremor, and then suddenly died. The reaction was attributed to either amantadine alone, or to amantadine and pramipexole. The woman started receiving pramipexole 0.125mg three times daily; after 1 week, her dosage was titrated up to 0.25mg [frequency not stated] and propranolol was added to her therapy. However, her tremor persisted 2 weeks later; amantadine 100mg twice daily was added to her treatment and her propranolol dosage was doubled. Her tremor had improved 1 week later; however, she failed to mention that she had also developed ataxic gait after amantadine initiation [time to reaction onset not stated]. She was taken to an emergency room (ER) with severe general malaise 4 days later. After a sleepless night in the ER, she was admitted to a ward the following morning. She had a BP of 188/94mm Hg, generalised areflexia, difficulties standing and walking, and exhibited intermittent spontaneous generalised myoclonus. Further tests revealed intention tremor, ataxia and dysmetria of both legs. An exaggerated action tremor of her trunk and limbs was noted whenever she tried rising from bed. Symptoms were ascribed to metabolic or toxic encephalopathy, with myoclonus and cerebellar ataxia. Laboratory investigations showed the following levels: haemoglobin 7.4 g/dL, creatinine 5.5 mg/dL, potassium 4.4 mEq/L and ALT 28 U/L. Nonspecific white matter changes were evident on brain MRI. A druginduced reaction was considered. Pramipexole was discontinued and the woman’s amantadine dosage was decreased to 100 mg/day. She did not sleep during the first night and became mildly confused before her amantadine dose the following morning. She seemed irritable around noon and was unable to recognise her son. After an episode of upward gazing 0.5 hours later, she suddenly became motionless; however, her son considered her to be exhausted and did not notify the doctors. Around 2:50pm, she was found dead by a nurse. No impairment of cardiac contractility was noted on emergency ultrasound immediately following resuscitation. Author comment: "The toxic manifestations include progressive ataxic gait, tremor, myoclonus, and rapid mental change followed by sudden death which is most likely due to amantadine-induced cardiac arrhythmia . . . However, the synergic effect of amantadine and pramipexole should be considered because theoretically it may contribute to the fatal outcome in our patient." Hong C-T, et al. Fatal intoxication using amantadine and pramipexole in a uremic patient. Acta Neurologica Taiwanica 17: 109-111, No. 2, Jun 2008 801117538 Taiwan

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Reactions 30 Aug 2008 No. 1217