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Symptomatic amyloid-related imaging abnormalities in an APOE ε4/ε4 patient treated with aducanumab.

  • Author(s): VandeVrede, Lawren
  • Gibbs, Daniel M
  • Koestler, Mary
  • La Joie, Renaud
  • Ljubenkov, Peter A
  • Provost, Karine
  • Soleimani-Meigooni, David
  • Strom, Amelia
  • Tsoy, Elena
  • Rabinovici, Gil D
  • Boxer, Adam L
  • et al.
Abstract

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.

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