Submitted by Brian M. Trotta, MD, University of Virginia Department of Radiology, Charlottesville, VA.
A 70-year-old male presents with a history of increasing headaches and confusion.
What is the most likely diagnosis?
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There is confluent T2/FLAIR signal abnormality within the right temporal, parietal, occipital, and posterior frontal lobe with a smaller focus in the left middle temporal lobe. There is associated mass effect with effacement of the adjacent cerebral sulci and mild right to left midline shift. Postcontrast images demonstrate no abnormal enhancement. Select images from a gradient-echo image demonstrate numerous foci of low-signal susceptibility artifact in the right temporal lobe.
Cerebral amyloid angiopathy (CAA) is a cerebrovascular disorder characterized by β-amyloid deposition within the media and adventitia of small- and medium-sized vessels of the cerebral hemispheres. Cases are generally sporadic, but hereditary forms may occur. Sporadic cases are much more common in the elderly. With age, the prevalence of CAA increases to approximately 75% of patients older than age 90.
Many patients with CAA are asymptomatic, but those who present acutely have a stroke-like clinical presentation secondary to intracranial hemorrhage. Alternatively, patients who present with chronic symptoms tend to have a clinical picture of dementia. CAA is also frequently associated with Alzheimer dementia with approximately 40% of CAA patients with dementia showing changes of Alzheimer dementia at autopsy, and 90% of patients with Alzheimer dementia demonstrating changes of CAA at autopsy. The natural history of CAA is recurrent hemorrhages and progressive cognitive decline.
Definitive diagnosis of CAA requires histologic analysis, which is impractical as most cases do not demonstrate a lesion, which is amenable to biopsy. Therefore, familiarity with the imaging features of CAA is important to ensuring an accurate diagnosis and proper treatment. As patients usually present with stroke-like symptoms, computed tomography (CT) is the imaging evaluation of choice to determine the presence or absence of hemorrhage. If intracranial hemorrhage is present in a cortical-subcortical location suspicious for CAA, magnetic resonance imaging (MRI) should be obtained, including a gradient echo sequence. Gradient echo images should demonstrate foci of signal loss in a cortical-subcortical distribution, which correlates with hemosiderin deposition from chronic microhemorrhages. The microhemorrhages occur in the same anatomic distribution as β-amyloid deposition within the vessels. Microhemorrhages are less common in the brainstem, cerebellum, and deep gray nuclei. In addition, most cases will also show significant cerebral atrophy.
Much less common morphologic varieties of CAA include a mass-like lesion termed an amyloidoma and a leukoencephalopathic form with diffuse white matter involvement as seen in the patient in this case. The amyloidoma form demonstrates a strongly enhancing mass with minimal mass effect, while the leukoencephalopathic form demonstrates confluent white matter hyperintensities on T2/FLAIR images. Both forms usually also demonstrate classic cortical-subcortical microhemorrhages, which serve as a clue to the diagnosis. Patients who demonstrate a subacute worsening of symptoms may have an inflammatory subtype of the leukoencephalopathic form with increased surrounding vasogenic edema. This subtype has termed cerebral amyloid inflammatory vasculopathy and is responsive to steroids. The differential for confluent white-matter signal abnormality is long, including demyelination, ischemia, infarction, infection, and edema, so CAA should be considered in cases associated with cortical-subcortical hemorrhages and a history of dementia.
As there is currently no treatment, which has been shown to halt or reverse β-amyloid deposition, care is instead focused on minimizing the risk of hemorrhage, including possible discontinuation of anticoagulation, which has been shown to increase the risk of intracranial hemorrhage in patients with CAA. In the small subset of patients who have an acute inflammatory form, such as this patient, steroids are often effective. This patient was treated with steroids and showed significant improvement clinically as well as on follow-up imaging.