Wischnewsky spots relate to ketosis/ketoacidosis regardless of the cause of death – A systematic autopsy study

Wischnewsky spots are considered strongly associated with postmortem diagnosis of hypothermia with an unclear pathophysiology. Recent studies have suggested an association between Wischnewsky spots and diabetic ketoacidosis, yet no systematic data exist about Wischnewsky spots in other ketotic states besides hypothermia. To elucidate the pathogenesis of Wischnewsky spots, we studied their presence in relation to ketosis/ketoacidosis, glucose, urine catecholamines, and toxicological factors. We included all medicolegal autopsies (n = 1903) with an ancillary glucose metabolism assay in the database of Forensic Medicine Unit, Finnish Institute for Health and Welfare, Oulu, Finland in 2019-2023. Cases were divided into hypothermia deaths, diabetes-related deaths, alcohol-related deaths, and other causes of death. The presence and extent of Wischnewsky spots were estimated from the autopsy reports. Concentrations of β-hydroxybutyric acid (BHB), glucose, ethanol, acetone, isopropanol, urinary adrenaline and noradrenaline, and the presence of cyclooxygenase-1 inhibitors were assessed. Mean BHB concentrations were higher with sparse, moderate, or extensive Wischnewsky spots compared with those with no Wischnewsky spots documented. Odds ratios for Wischnewsky spots were 3.7 with BHB concentration ≥ 0.5 mmol/L, 3.6 with BHB concentration > 2.5 mmol/L, 4.8 with positive blood acetone, 3.6 with positive urine acetone, and 2.2 with adrenaline-noradrenaline ratio > 0.1876. Our findings showed a clear, concentration-dependent association between BHB concentration and the presence of Wischnewsky spots irrespective of the underlying cause of death. Our results indicate that Wischnewsky spots are linked to disturbances in glucose metabolism, not exclusively to hypothermia, highlighting the diagnostic importance of postmortem BHB measurement.