C49-26 Donanemab-induced ARIA-H: A Case of Seizures and Radiographic PRES in an Elderly Alzheimer’s Patient

Introduction Donanemab is an emerging anti-amyloid monoclonal antibody approved for the treatment of Alzheimer’s disease. Although it has shown efficacy in slowing cognitive decline, it is associated with amyloid-related imaging abnormalities (ARIA), including vasogenic edema (ARIA-E) and cerebral microhemorrhages (ARIA-H). We present a case of severe ARIA-H with new-onset seizures in a patient undergoing donanemab therapy. Case Description A 75-year-old female with Alzheimer’s dementia and hypertension on donanemab four-dose infusions since February 2025, presented after a ground-level fall with head trauma and brief loss of consciousness. Her family reported two weeks of worsening confusion, word-finding difficulty, and imbalance. In the emergency department, she experienced a witnessed generalized tonic-clonic seizure lasting two minutes. She was administered IV levetiracetam and transferred to the ICU. Shortly after arrival, she became bradycardic and hypotensive, followed by recurrent generalized seizures requiring escalating doses of IV midazolam and endotracheal intubation for airway protection. Initial CT head demonstrated a small left insular subarachnoid hemorrhage and bilateral posterior subcortical hypoattenuation suggestive of PRES. MRI of the brain revealed multifocal vasogenic edema and petechial hemorrhages, consistent with severe ARIA-H. Continuous EEG showed left hemispheric cerebral dysfunction with high seizure propensity. She was treated with a 5-day course of IV methylprednisolone followed by a prolonged oral steroid taper. Donanemab was discontinued, and monthly MRIs were planned. She demonstrated functional improvement with physical therapy and was discharged home with home PT/OT and close neurology follow-up. Discussion This case highlights a severe, symptomatic manifestation of ARIA-H associated with donanemab therapy, presenting with new-onset seizures and radiographic features of PRES. While most ARIA events are asymptomatic and self-limited, this case underscores the potential for acute neurologic decompensation requiring ICU-level care. As anti-amyloid therapies gain widespread use, clinicians should maintain a high index of suspicion for ARIA in patients with altered mental status or seizures and ensure close radiologic surveillance during treatment. This abstract is funded by: None