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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.