UCSF

INTRODUCTION: Amyloid-related imaging abnormalities (ARIA) are a common, dose-dependent effect of amyloid-targeting antibodies, strongly associated with the apolipoprotein E (APOE) ε4 allele. METHODS: We describe the clinical course and management of a 66-year-old white male (APOE ε4/ε4) enrolled in an observational study that included amyloid and tau positron emission tomography (PET), who received aducanumab through the ENGAGE clinical trial. RESULTS: Acute symptoms included headache and encephalopathy, and magnetic resonance imaging revealed ARIA-E and ARIA-H. Malignant hypertension and epileptiform activity were treated with nicardipine and levetiracetam. Subsequent clinical/imaging worsening prompted a course of methylprednisolone. Symptoms and ARIA-E resolved over 6 months, while ARIA-H persisted. Quantitative analysis of interval amyloid PET showed reduced signal in pre-existing areas but increased signal posteriorly; while tau PET showed increased signal overall. DISCUSSION: In an APOE ε4/ε4 patient, ARIA symptoms were accompanied by malignant hypertension and epileptiform activity, and pulsed steroids reversed edema. Studies from larger cohorts may clarify the optimal treatment and pathophysiology of ARIA.