We report a case of recurrent posterior reversible encephalopathy syndrome (PRES) secondary to uncontrolled hypertension, initially misdiagnosed as osmotic demyelination syndrome (ODS) due to concomitant hyponatremia and overlapping radiologic features. PRES is a neurotoxic state characterized by vasogenic edema predominantly affecting the parieto-occipital regions, but in some cases, it may extend to deep gray matter and the brainstem, leading to diagnostic confusion with ODS.

A 61-year-old chronic alcoholic woman with three days of poor oral intake presented with acute mental deterioration and a generalized tonic–clonic seizure. She was drowsy but followed commands, showing generalized weakness. Brain MRI revealed extensive bilateral T2/FLAIR hyperintensities involving the brainstem, cerebellum, thalamus, mammillary body, lentiform nucleus, and periventricular white matter. Laboratory tests showed severe hyponatremia (Na 120 mEq/L), hypokalemia (K 2.8 mEq/L), and metabolic alkalosis. EEG demonstrated diffuse background slowing. She received intravenous saline, high-dose thiamine, and potassium supplementation, with sodium corrected gradually to 134 mEq/L over 48 hours. Despite persistently elevated blood pressure (>180 mmHg systolic), symptoms improved with antihypertensive therapy, and follow-up MRI showed near-complete resolution.

Two months later, follow-up MRI revealed aggravation of extensive FLAIR/T2 hyperintensities, followed by severe headache and hypertensive crisis (194/122 mmHg) after poor medication adherence. Laboratory findings were normal, and symptoms rapidly resolved after blood pressure control.

This case underscores a diagnostic pitfall where PRES mimics ODS in patients with hyponatremia and diffuse brain lesions. The reversible course and recurrence associated with hypertension strongly support PRES rather than ODS. In such cases, prompt recognition and aggressive management of treatable causes (particularly hypertension) are crucial to prevent neurological sequelae.