Amyloid related imaging abnormalities (ARIA)

Amyloid related imaging abnormalities (ARIA) represent a variety of imaging features identified in patients with Alzheimer disease being treated with novel amyloid lowering therapies such as the monoclonal antibodies bapineuzumab, solanezumab and aducanumab ^1-4. 

Clinical presentation

In most instances, ARIA is detected incidentally on imaging. Some patients describe various symptoms related, presumably, to cerebral edema and irritation including headaches, vomiting, confusion, and gait disturbance ⁴. 

Pathology

Although the mechanism underlying these phenomena remains to be fully understood they are believed to be related to the breakdown of the blood-brain barrier as a result of the mobilization of the amyloid previously deposited in blood vessels ^1,2. 

The likelihood of developing hemorrhagic lesions correlates with the dose of anti-amyloid drug, the number of APOE ε4 alleles, also known to correlate with increased risk of cerebral amyloid angiopathy, as well as concurrent use of antithrombic ages ^3,5. 

Radiographic features

Amyloid related imaging abnormalities (ARIA) are primarily identified on MRI, although more pronounced changes would be expected to be visible also on CT. The distribution of changes correlates to the most active areas of amyloid removal ⁵. 

MRI

ARIA is divided into two subtypes, based on the presence of edema and hemorrhages although they frequently co-exist ¹. 

ARIA-E

ARIA-E (e for edema) is characterized by the presence of ¹:

• parenchymal edema (ARIA-E edema)

  • high T2/FLAIR signal involving subcortical white matter and/or cortex

  • no abnormal diffusion restriction

  • no parenchymal enhancement, but subtle overlying leptomeningeal/cortical enhancement may be seen

• sulcal effusions (ARIA-E effusions)

  • high FLAIR signal (non-attenuating) in sulci often overlying an area of parenchymal edema

Although ARIA-E can occur bilaterally, it is most frequently (~2/3) unilateral ¹. 

ARIA-H

ARIA-H (h for hemorrhage) is usually seen in combination with ARIA-E and is characterized by the presence of ^1,4:

• parenchymal microhemorrhages (most common)

• sulcal/leptomeningeal hemosiderin deposits

Treatment and prognosis

No treatment is usually required, other than withholding further treatment with the amyloid-lowering agent ⁴. In occasional cases, steroids have been given to reduce cerebral edema ⁴.

Both parenchymal edema and sulcal effusions forms of ARIA-E are usually transient resolving over a number of months ¹. Blood products, in contrast, usually do not.

Differential diagnosis

• inflammatory cerebral amyloid angiopathy

  • the imaging features of ARIA are essentially identical, with the only real distinguishing feature being clinical context; namely, ARIA occurs in individuals being treated with amyloid lowering agents

• posterior reversible encephalopathy (PRES)

  • similar, usually posterior, can involve deep grey matter

  • usually in the setting of severe hypertension or other risk factors

  • usually no microhemorrhages

• subarachnoid hemorrhage

  • sulcal effusions can mimic subarachnoid blood

• meningitis

  • sulcal effusions can mimic sulcal pus

• cerebral infarction

  • diffusion restriction during the acute phase

  • prominent enhancement during the sub-acute phase

• perilesional edema (e.g. around metastasis, primary tumor, abscess)

  • underlying lesion usually visible