Validation of Clinical-Radiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-related Inflammation

Introduction: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a disease subtype characterized by rapidly progressive cognitive decline, seizures, headaches, T2-hyperintense MRI lesions, and neuropathologic evidence of CAA-associated vascular inflammation. CAA-ri is an important diagnosis to reach in clinical practice, as many patients respond to immunosuppressive therapy. Definitive diagnosis of CAA-ri generally requires brain biopsy, however, highlighting the importance of developing noninvasive diagnostic criteria. Objectives: To test the sensitivity and specificity of modified criteria (Table 1) for possible and probable CAA-ri in groups of subjects with histologically proven CAA-ri and non-CAA-ri. Methods: After refining previously proposed clinical- radiological criteria we retrospectively analyzed clinical charts and MRI FLAIR and gradient-echo scans obtained from 17 subjects with pathologically confirmed CAA-ri and 37 control subjects with pathologic diagnosis of non-inflammatory CAA. The control group was further divided into those with past intracerebral hemorrhage (ICH) (n=21) and those with cerebral microbleeds (CMB) only and no history of ICH (n=16). Results: In the CAA-ri group 14/17 (82.4%) met criteria for both probable and possible CAA-ri. One (4.7%) of the subjects in the control CAA-ICH group (n=21) met the criteria for possible and none met criteria for probable CAA-ri. In the control CAA-no ICH group 1/16 (6.25%) and 11/16 (68.75%) met criteria for probable and possible CAA-ri respectively. This yields sensitivity and specificity of 82% and of 97.3% respectively for the probable criteria and sensitivity and specificity of 82% and 67.6% respectively for the possible criteria. Conclusions: Our data suggest that a reliable diagnosis of CAA-ri can be reached from basic clinical and radiographic information alone with good sensitivity and excellent specificity.