Case of the Week
Section Editors: Matylda Machnowska1 and Anvita Pauranik2
1University of Toronto, Toronto, Ontario, Canada
2BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
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April 8, 2021
Cerebral Amyloid Angiopathy (CAA) Associated with Inflammation (Inflammatory CAA)
- Background:
- Cerebral amyloid angiopathy (CAA) is characterized by deposition of amyloid-beta in the media and adventitia of cortical and leptomeningeal arteries.
- CAA can present on imaging as CAA (common), amyloidoma (uncommon), or inflammatory CAA (rare).
- Two types of inflammatory responses are amyloid-beta-related angiitis (ABRA) ("an angiodestructive process characterized by a vasculitic transmural, often granulomatous, inflammatory infiltration") and CAA-related inflammation (CAA-RI) ("an inflammatory reaction that surrounds amyloid-laden vessels, without angiodestructive features"). In 2018, Corovic et al observed 73% ABRA, 51% CAA-RI, and 23% both subtypes in pathologic studies among 213 patients with inflammatory CAA.
- Clinical Presentation:
- While CAA often remains clinically occult, it most commonly presents with lobar intracerebral hemorrhage in an older normotensive patient when symptomatic.
- The inflammatory form of CAA is much less frequently complicated by intracranial hemorrhage and patients can present with multiple nonspecific neurologic symptoms including subacute cognitive decline, seizures, and headaches.
- Leptomeningeal disease with or without infiltrative white matter process is significantly more frequent in patients with ABRA and CAA-RI than those with CAA, whereas lobar hemorrhage is more frequent in patients with CAA.
- Patients with CAA-RI and ABRA are generally younger than those with CAA, which is usually seen in patients older than 60.
- Key Diagnostic Features:
- MRI: Key imaging findings that distinguish typical CAA from CAA-RI and ABRA:
- CAA: Lobar hemorrhages of different ages (best diagnostic clue); peripherally located cortical/subcortical microbleeds
- CAA-RI and ABRA: Evolving and sometimes migratory areas of lobar white matter T2 prolongation or diffuse lobar edema; leptomeningeal enhancement (common); peripherally located tiny foci of cortical/subcortical microbleed and superficial siderosis; focal, masslike enhancement and intracerebral lobar hemorrhage (uncommon)
- CSF analysis: In 2018, Corovic et al reported that 83% of patients with inflammatory CAA had an elevated protein of >45 mg/dL, 44% had an elevated CSF white cell count of >5 cells/mm3, and 17% had oligoclonal bands. Specific anti-amyloid-beta antibodies can be identified from the CSF of patients with biopsy-proven inflammatory CAA. These findings suggest an immune and humoral response being responsible for the findings of inflammatory CAA.
- MRI: Key imaging findings that distinguish typical CAA from CAA-RI and ABRA:
- Differential Diagnoses:
- Extrapontine osmotic demyelination: Areas of lobar T2 prolongation are usually bilateral and symmetric in cases of extrapontine osmotic demyelination. Associated electrolyte abnormalities characteristically with rapid correction of hyponatremia.
- Posterior reversible encephalopathy syndrome (PRES): Areas of lobar T2 prolongation are usually bilateral and symmetric in cases of PRES, and it is often associated with known triggers including hypertension, and drug exposures.
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Other types of vasculopathy/vasculitis: Often younger presentation; may be associated with areas of hemorrhage, infarction, and vascular abnormalities on angiographic imaging
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Hypertensive vasculopathy (chronic hypertension): Generally central, deep gray matter, and brainstem microbleeds and chronic periventricular and deep white matter areas of T2 prolongation, which do not resolve over time
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CVA: Expect restricted diffusion.
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Sequelae of small vessel ischemic disease (leukoariosis): Not expected to resolve on short-term interval imaging
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Toxic-metabolic or drug-related etiologies: Findings of areas of T2 prolongation are usually bilateral and symmetric in cases of toxic-metabolic or drug-related etiologies, and may be associated with relevant history of exposure.
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CADASIL: Usually more extensive persistent white matter areas of T2 FLAIR hyperintense signal, involving the anterior temporal regions and external capsules preferentially
- Treatment:
- As ABRA or CAA-RI respond to immunosuppressive therapy, when neurologic and neuroradiologic findings are consistent with ABRA or CAA-RI, the physician should consider starting an appropriate immunosuppressive treatment even in the absence of pathologic confirmation.
- If a biopsy is requested, the surgeon should direct the biopsy to the leptomeningeal and gray-white junction.
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