Non-hyponatremia-associated osmotic demyelination syndrome: an analysis of published cases.

Background Osmotic demyelination syndrome (ODS), formerly known as central pontine myelinolysis, is classically associated with rapid correction of hyponatremia. However, ODS has also been reported in normo- or hypernatremic patients, often linked to other metabolic or systemic risk factors. Despite numerous single-case reports, systematic data on non-hyponatremia ODS remain scarce. This study aimed to summarize clinical characteristics, possible causes, and outcomes of ODS in patients without hyponatremia.Methods A systematic PubMed search was conducted for case reports on ODS or central pontine myelinolysis published between January 1990 and December 2024. Cases were included if serum sodium was ≥135 mmol/L. Extracted data comprised demographics, laboratory parameters, risk factors, causes of ODS, imaging findings, treatment and outcome. Statistical analyses were descriptive and performed using JASP 0.95.0.Results A total of 169 cases from 161 publications were identified. The mean age was 42 years, and 44% were female. MRI confirmed ODS in 96% of cases. Median sodium concentration was 140 mmol/L, with 42% showing hypernatremia. Hypokalemia was present in 24% and diabetes mellitus in 28%. Common risk factors for ODS included alcohol abuse (26%), liver disease (18%) and malnutrition (11%). Treatment approaches were heterogeneous 28 patients received glucocorticoids, but immunoglobulins or plasmapheresis were rarely used. Full recovery occurred in 47%, while mortality was 9.5%.Conclusions ODS can occur in the absence of hyponatremia, particularly in patients with electrolyte disturbances or systemic risk factors. The condition remains underrecognized and heterogeneously managed. Awareness of non-hyponatremia ODS and standardized treatment protocols are needed to improve patient outcomes.