eMedicine Specialties > Neurology > Neuro-vascular Diseases
Cerebral Amyloid Angiopathy: Differential Diagnoses & Workup
Updated: Aug 20, 2008
- Overview
- Differential Diagnoses & Workup
- Treatment & Medication
- Follow-up
- Multimedia
Differential Diagnoses
Other Problems to Be Considered
Anticoagulation, complications
Blood dyscrasias
Bronchogenic carcinoma
Choriocarcinoma
CNS tumors, primary and metastatic
Fibrinolysis, complications
Hypertension
Malignant melanoma
Renal cell carcinoma
Toxicity, cocaine and other sympathomimetic agents
Vascular malformations
Neuroimaging of vascular malformations and hematomas of the brain
Workup
Laboratory Studies
- No specific laboratory findings are diagnostic of cerebral amyloid angiopathy (CAA).
- Some patients may have CSF abnormalities: increased protein, decreased soluble β-amyloid or ApoE.
- The severity of the angiopathy is associated with ApoE polymorphism. The ApoE e4 and e2 alleles are risk factors for CAA.
- The ApoE e2 allele also confers an increased risk of intracranial hemorrhage (ICH) in patients with CAA. The ApoE e4 allele is associated with earlier onset of first hemorrhage and carries a significant risk of concomitant AD.3
- Patients with lobar ICH and the e2 or e4 allele have a greater risk of early recurrence.
- These tests lack sensitivity and specificity and are not indicated as screening or diagnostic procedures. However, they may be helpful prognostic tools in identifying patients with a greater risk of early recurrence.
- In cases of CAA-related ICH, laboratory studies should rule out other possible etiologies.
- Genetic evaluation can be considered, especially in those with a family history of CAA.
Imaging Studies
- CT scan
- A single lobar hemorrhage with superficial location and cortical involvement with or without local extension to the subarachnoid and intraventricular spaces is suggestive of CAA-related hemorrhage. Evidence of multiple hemorrhages restricted to lobar regions may be present.
- Hemorrhages are more common in the frontal and parietal lobes, involving the cortex and subcortical white matter. Over time, several lobes may be involved. Deep central gray nuclei, the corpus callosum, and the cerebellum are sometimes affected. CAA is rarely the cause of putaminal, thalamic, or brain stem hemorrhage.
- Pure subarachnoid, intraventricular, and subdural hemorrhages can be seen but are rare. CAA should never be assumed to be the cause of an isolated subarachnoid hemorrhage unless all other causes, particularly aneurysmal, have been excluded.
- Patients with CAA-associated dementia have a leukoencephalopathy similar to that seen in Binswanger disease. Atrophy can also be detected, particularly in patients with cognitive impairment and a history of prior hemorrhage.
- MRI
MRI Brain GRE 3.0 Tesla
Top: Multiple scattered microbleeds in multiple vascular territories in patient with hyperhomocysteinemia and methylene-tetrahydrofolate reductase mutation.
Middle: Acute parenchymal hematoma with typical appearance of right occipital microbleed and left parietal chronic microhemorrhage.
Bottom: Microbleeds involving multiple lobes. Chronic hemorrhage in the left parietal lobe with typical slit-like appearance.
- MRI may show evidence of multiple cortical and subcortical large and small petechial hemorrhages, even in patients without a history of previous hemorrhage. In asymptomatic patients, clinically silent microhemorrhages may serve as a marker of disease progression.
- MRI gradient-echo (GRE) sequences show evidence of hemosiderin deposition that corresponds to old hemorrhages. In patients who present with lobar hemorrhages, evidence of old petechial bleeds can help in the diagnosis of CAA.
- Punctate (usually <5 mm), round hypointensities on GRE, termed microbleeds are frequently identified in white matter. These cerebral microhemorrhages are often present in amyloid angiopathy, but are not diagnostic of amyloid pathologically. Any conclusions regarding the significance of cerebral microbleeds must be interpreted given the individual patient or population evaluated.
- Microbleeds may be associated with hemorrhagic transformation of ischemic stroke. Microbleeds may be more common in patients with hypertension, but no characteristic pattern occurs in the distribution of microbleeds. Microbleeds may suggest a hemorrhage-prone angiopathy involving brain parenchyma distant from identified microbleeds.
- The presence, or number, of microbleeds may impact decisions to administer thrombolytic, anticoagulant, or antiplatelet therapy.
- A higher number of ICH at baseline on GRE is associated with a higher risk of future ICH, subsequent cognitive impairment, loss of independence, and death.
- Leptomeningeal enhancement is seen in patients with associated vasculitis.
- Angiography
- Angiographic findings are abnormal only in rare cases of CAA-related vasculitis. Specificity and positive predictive value in such cases is <30%. Definite diagnosis requires brain biopsy (sensitivity 53%, negative predictive value 70%).
- Given that some of the features of CAA and vasculitis are similar, a high index of suspicion is required. Angiography should be considered in patients with a history of hemorrhages or ischemic strokes with rapid cognitive decline (over weeks or a few months), prominent headaches, and seizures.
- Positron-emission tomography (PET)
- Cortical retention of Pittsburgh Compound B (binds β -amyloid) may serve as an in vivo marker of CAA in humans.
Other Tests
EEG may be diffusely abnormal, but it usually does not show evidence of seizure focus.
Histologic Findings
Histologic examination is required for definitive diagnosis. Pathologic samples are obtained from hematoma evacuation, cortical biopsy, or postmortem specimens. The disease process may be diffuse, so pathologic data may be lacking even in biopsy cases.
The presence of vascular amyloid is a sensitive marker for CAA-related hemorrhage. β-amyloid consists of twisted β-sheet fibrils in vessel wall. It is a homogenous, intensely eosinophilic material that gives a smudged appearance by light microscopy. When stained with Congo red and visualized under polarized light, it gives a characteristic yellow-green (ie, apple green) birefringence. When thioflavin T and S are used and visualized with ultraviolet light, amyloid appears fluorescent.
The presence of fibrinoid necrosis in amyloid-laden vessels is relatively specific for CAA-related ICH. CAA, which involves cortical and leptomeningeal vessels, is most common in the parietal and occipital lobes. Parenchymal features found in the brains of patients with CAA include patchy demyelination and loss of white matter, cortical hemorrhages and infarcts, and neuritic plaques with or without neurofibrillary tangles. Patients with CAA have been found with a progressive increase in white matter lesions: this may suggest a progressive microangiopathy leading to incident lobar hemorrhage. Most patients with CAA-related ICH do not have Alzheimer disease.
More on Cerebral Amyloid Angiopathy |
| Overview: Cerebral Amyloid Angiopathy |
 Differential Diagnoses & Workup: Cerebral Amyloid Angiopathy |
| Treatment & Medication: Cerebral Amyloid Angiopathy |
| Follow-up: Cerebral Amyloid Angiopathy |
| Multimedia: Cerebral Amyloid Angiopathy |
| References |
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References
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Further Reading
Keywords
cerebrovascular amyloidosis, cerebral amyloid angiopathy, congophilic angiopathy, dysphoric angiopathy, β-amyloid, beta-amyloid, Alzheimer's disease, intracranial hemorrhage, ICH, dementia, transient neurologic events, hereditary cerebral hemorrhage with amyloidosis, hereditary cerebral hemorrhage with amyloidosis-Dutch type, hereditary cerebral hemorrhage with amyloidosis-Icelandic type, HCHWA, cerebral microbleeds, stroke, ischemic strokes
