Diabetic ketoacidosis, refractory hypokalemia, and acquired arginine vasopressin resistance preceding osmotic demyelination syndrome: A possible pathophysiological cascade

Abstract

Osmotic demyelination syndrome (ODS) is classically linked to rapid correction of chronic hyponatremia, but dynamic 
osmotic changes during treatment of diabetic ketoacidosis (DKA) may also cause ODS. A 22-year-old man with 
schizophrenia receiving aripiprazole and clozapine presented with DKA after prolonged poor intake and 30-kg weight 
loss. Blood glucose at presentation was 399 mg/dL and fell to 146 mg/dL within 2 h. Sodium rose from 140 to 
148.9 mmol/L within 11 h and peaked at 149.4 mmol/L, while potassium reached 2.0 mmol/L and remained severely 
low through early 18 December despite replacement. After glycemic control, persistent dilute urine despite serum 
hyperosmolality suggested acquired partial arginine vasopressin resistance. He subsequently developed hypophonia, 
dysarthria, rigidity, bradykinesia, tremor, urinary incontinence, and gait impairment. Brain magnetic resonance imaging 
showed changes suggestive of ODS. The sequence supports a cascade linking DKA, profound potassium depletion, 
insulin-related intracellular shift, hypokalemia-associated concentrating failure, hypotonic water loss, and cumulative 
hyperosmolar stress to ODS.