Acute toxic leucoencephalopathy following protonitazene ingestion

BACKGROUND: Distribution of illicit counterfeit alprazolam containing the highly potent synthetic opioid-receptor agonist protonitazene recently resulted in a number of severe overdoses in Ireland. We report three cases that presented to our hospital, within 6 weeks of one another, following ingestion of illicitly-sourced alprazolam. All cases demonstrated clinical and radiological findings consistent with acute toxic leucoencephalopathy. CASE REPORTS: A 19-year-old male ingested several tablets of counterfeit alprazolam. Magnetic resonance imaging (MRI) demonstrated mild white matter changes consistent with acute toxic leucoencephalopathy. He was extubated after 6 days and made a full neurological recovery by Day 22. A 30-year-old male suffered an out-of-hospital cardiac arrest following ingestion of illicitly sourced alprazolam. MRI demonstrated extensive white matter changes in a distribution consistent with severe acute toxic leucoencephalopathy. There was no neurological recovery, and he passed away 30 days following presentation. A 36-year-old male was found surrounded by empty packaging of illicitly-sourced alprazolam. He was intubated and subsequent MRI demonstrated near-identical features to that of Case 2. He made no neurological recovery by Day 27 and passed away on Day 45. Analysis by gas chromatography-mass spectrometry identified protonitazene in the recovered tablets of Cases 1 and 2. Case 3 had no tablets available for analysis, though the empty alprazolam packaging was identical to that seen in Cases 1 and 2. CONCLUSION: These cases describe a trio of local protonitazene poisonings that were associated with the development of acute toxic leucoencephalopathy. Prognosis was poor but variable, with a correlation between radiological severity and neuroprognostication.