To describe a case of acute encephalopathy and seizure during donanemab infusion, highlighting the diagnostic challenge of determining whether hyponatremia resulted from fluid overload or an infusion-related reaction.

Donanemab, an anti-amyloid monoclonal antibody, has demonstrated efficacy in Alzheimer’s disease but may be complicated by amyloid-related imaging abnormalities (ARIA) and infusion-related reactions. Severe metabolic disturbances, such as hyponatremia, are rarely reported. Identifying their etiology is essential for guiding treatment and ensuring safety during therapy.

Case report of a 78-year-old woman with Alzheimer’s disease on donanemab who developed acute altered mental status and seizure during her fifth infusion. The patient was receiving donanemab under the modified dosing regimen used to reduce ARIA risk. Clinical presentation, laboratory data, imaging, and hospital course were reviewed.

During her fifth donanemab infusion, the patient developed hypotension, dyspnea, and tremulousness, followed by unresponsiveness and a generalized tonic-clonic seizure. CT suggested possible ARIA, but MRI showed no edema or hemorrhage. Serum sodium was 121 mEq/L. The patient had experienced mild symptoms during her previous infusion, consistent with a possible infusion reaction. Subsequently she reported marked thirst and was thought to have consumed more than 10 L of water, suggesting free-water overload on the background of an infusion-related stress response. She was treated with hypertonic saline, then managed with D5 and desmopressin for rapid sodium correction. Continuous EEG revealed no seizures. She returned to baseline cognition after sodium normalization (Na 136 mEq/L). Fever and mild leukocytosis resolved spontaneously.

This case highlights an infusion reaction to donanemab complicated by hyponatremia and seizure. The temporal pattern supports an infusion-related mechanism, with excessive free-water intake and transient ADH release likely contributing to hyponatremia. Clinicians should recognize that metabolic complications may accompany infusion reactions during anti-amyloid therapy and that not all neurologic events represent ARIA.