By Joseph E. Safdieh, MD
Vice Chair and Associate Professor, Weill Cornell Medical College
Dr. Safdieh reports no financial relationships relevant to this field of study.
SYNOPSIS: Refinement of the imaging criteria for cerebral amyloid angiopathy-related inflammation may increase sensitivity and specificity enough to forgo brain biopsy.
SOURCE: Auriel E, et al. Validation of clinicoradiological criteria for the diagnosis of cerebral amyloid angiopathy — Related inflammation. JAMA Neurol 2015; Dec 28 doi:10.1001/jamaneurol.2015.4078 [Epub ahead of print].
Cerebral amyloid angiopathy (CAA) is caused by deposition of amyloid in the cerebral blood vessels. It is a common cause of lobar intracranial hemorrhage as well as cerebral microbleeds in older patients. In a subset of patients with CAA, an immune response occurs, which leads to an inflammatory form of CAA (CAA-related inflammation, CAA-ri). CAA-ri manifests clinically with headaches, rapidly progressive cognitive decline, and seizures. It is in the differential diagnosis of rapidly progressive dementia, and although rare, as a treatable condition, it is critically important to diagnose promptly. Imaging can be helpful in suggesting the diagnosis, but at the current time, only a brain biopsy can confirm the diagnosis. Traditionally described imaging findings include asymmetric white matter hyperintensities extending to the subcortical white matter, as well as cerebral microbleeds or evidence of recent lobar intracerebral hemorrhage (ICH). Gadolinium enhancement and mass effect are variably present. Brain biopsy features confirming the diagnosis include the presence of amyloid deposition in cerebral vessels with associated infiltrate of inflammatory cells.
In this study, the authors proposed more refined imaging criteria for probable and possible CAA-ri and apply these criteria to a previously biopsied cohort of patients with confirmed CAA-ri to determine sensitivity and specificity of these refined diagnostic imaging criteria. The proposed revised imaging criteria include the current criteria but add magnetic resonance imaging evidence of cortical superficial siderosis as an additional criterion to demonstrate CAA changes in suspected CAA-ri. Possible vs probable CAA-ri are differentiated on the basis of asymmetric (probable CAA-ri) vs symmetric (possible CAA-ri) white matter hyperintensities. The authors assessed for the presence of clinical and imaging criteria for possible and probable CAA-ri in retrospectively diagnosed cohorts of patients with confirmed CAA-ri as well as CAA controls, both CAA with lobar ICH and CAA without lobar ICH (see Table 1).
Table 1. Criteria for the Diagnosis of CAA-ri |
|
Diagnosis |
Criteria |
|
Probable CAA-ri |
|
|
Possible CAA-ri |
|
|
ICH: intracerebral hemorrhage, MRI: magnetic resonance imaging, WMH: white matter hyperintensities |
|
The authors identified 17 patients with biopsy-confirmed CAA-ri, mean age 68. Of those patients, 14 met the proposed criteria for probable and possible CAA-ri, yielding a sensitivity of 82% for both criteria. In the control group having non-inflammatory CAA with lobar ICH, one of 21 (5%) fulfilled the criteria for possible CAA-ri, and none for probable CAA-ri. In the control group having noninflammatory CAA with no ICH, 11 of 16 (69%) met the criteria for possible CAA-ri, and one of 16 (6%) for probable CAA-ri. These findings yielded a specificity of 97% for the probable CAA-ri criteria and a specificity 68% for the possible CAA-ri criteria. The authors concluded that the criteria for probable CAA-ri have a high enough sensitivity and specificity (82% and 97%, respectively) that brain biopsy may be unnecessary if patients meet these criteria and treatment may be initiated earlier.
COMMENTARY
This important study adds to the literature on CAA-related inflammation, an important diagnosis to make, because treatment with immunosuppressive medications, such as methylprednisolone and cyclophosphamide, may be highly effective. Brain biopsy is an invasive procedure with associated morbidity and mortality, albeit low. If the diagnosis of CAA-ri can be made on the basis of clinical and imaging criteria alone, patients may be spared the need for biopsy. However, it is still important to consider other causes of progressive encephalopathy with asymmetric white matter changes, particularly, primary central nervous system (CNS) lymphoma. Initial response to steroids is typical of lymphoma, and without brain biopsy, it would be possible to misdiagnose lymphoma as CAA-ri. It would be very helpful in a future study if the authors can refine the specificity of the probable CAA-ri criteria by applying them to a cohort of patients with biopsy proven CNS lymphoma to determine whether there is enough specificity to use these criteria. Until that time, it would still be prudent to perform brain biopsy for patients with suspected CAA-ri.
Refinement of the imaging criteria for cerebral amyloid angiopathy-related inflammation may increase sensitivity and specificity enough to forgo brain biopsy.
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