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Original Investigation |

Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy–Related Inflammation

Eitan Auriel, MD, MSc1,2; Andreas Charidimou, MD, PhD1; M. Edip Gurol, MD, MSc1; Jun Ni, MD1; Ellis S. Van Etten, MD1; Sergi Martinez-Ramirez, MD1; Gregoire Boulouis, MD1; Fabrizio Piazza, PhD2,3; Jacopo C. DiFrancesco, MD, PhD2,3; Matthew P. Frosch, MD, PhD4; Octάvio M. Pontes-Neto, MD, PhD1; Ashkan Shoamanesh, MD1,5; Yael Reijmer, PhD1; Anastasia Vashkevich, BA1; Alison M. Ayres, BA1; Kristin M. Schwab, BA1; Anand Viswanathan, MD, PhD1; Steven M. Greenberg, MD, PhD1,2
[+] Author Affiliations
1The J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston
2The Inflammatory Cerebral Amyloid Angiopathy and Alzheimer’s Disease βiomarkers International Network, University of Milano-Bicocca, Monza, Italy
3Milan Center for Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy
4Neuropathology Service, C. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital and Harvard Medical School, Boston
5Population Health Research Institute, McMaster University, Hamilton, Ontario, Canada
JAMA Neurol. 2016;73(2):197-202. doi:10.1001/jamaneurol.2015.4078.
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Importance  Cerebral amyloid angiopathy–related inflammation (CAA-ri) is an important diagnosis to reach in clinical practice because many patients with the disease respond to immunosuppressive therapy. Reliable noninvasive diagnostic criteria for CAA-ri would allow some patients to avoid the risk of brain biopsy.

Objective  To test the sensitivity and specificity of clinical and neuroimaging-based criteria for CAA-ri.

Design, Setting, and Participants  We modified the previously proposed clinicoradiological criteria and retrospectively analyzed clinical medical records and magnetic resonance imaging fluid-attenuated inversion recovery and gradient-echo scans obtained from individuals with CAA-ri and noninflammatory CAA. At 2 referral centers between October 1, 1995, and May 31, 2013, and between January 1, 2009, and December 31, 2011, participants included 17 individuals with pathologically confirmed CAA-ri and 37 control group members with pathologically confirmed noninflammatory CAA. The control group was further divided into those with past lobar intracerebral hemorrhage (ICH) (n = 21) and those with cerebral microbleeds only and no history of ICH (n = 16). The dates of our analysis were September 1, 2012, to August 31, 2015.

Main Outcomes and Measures  The sensitivity and specificity of prespecified criteria for probable CAA-ri (requiring asymmetric white matter hyperintensities extending to the subcortical white matter) and possible CAA-ri (not requiring the white matter hyperintensities to be asymmetric).

Results  The 17 patients in the CAA-ri group were a mean (SD) of 68 (8) years and 8 (47%) were women. In the CAA-ri group, 14 of 17 (82%) met the criteria for both probable and possible CAA-ri. In the control group having noninflammatory CAA with lobar ICH, 1 of 21 (5%) met the criteria for possible CAA-ri, and none met the criteria 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 1 of 16 (6%) met the criteria for probable CAA-ri. These findings yielded a sensitivity and specificity of 82% and 97%, respectively, for the probable criteria and a sensitivity and specificity of 82% and 68%, respectively, for the possible criteria.

Conclusions and Relevance  Our data suggest that a reliable diagnosis of CAA-ri can be reached from basic clinical and magnetic resonance imaging information alone, with good sensitivity and excellent specificity.

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Figure 1.
Neuroimaging Features of Probable and Possible Cerebral Amyloid Angiopathy–Related Inflammation (CAA-ri)

Both individuals (a 75-year-old woman in A and B and an 80-year-old woman in C and D) had similar findings (cortical superficial siderosis8) on gradient-echo (GRE) images. The fluid-attenuated inversion recovery (FLAIR) image in A meets the criteria for probable CAA-ri, and the FLAIR image in C meets the criteria for possible CAA-ri. Neuropathological data were positive for CAA-ri in A and B and were negative for CAA-ri in C and D.

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Figure 2.
Characteristic Pathological Findings of Sporadic Cerebral Amyloid Angiopathy (CAA) and a CAA-Related Inflammation Case From Brain Biopsy Samples Stained With Anti–β-Amyloid Antibodies (Brown)

A, Dense amyloid deposition spans the entire vessel wall in a small cortical vessel without any associated inflammatory cells within the vessel wall or in the perivascular space. B, Inflammatory perivascular cell infiltrate surrounds an amyloid-laden small vessel. Scale bar = 100 μm.

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Figure 3.
Pretreatment and Posttreatment Fluid-Attenuated Inversion Recovery (FLAIR) Images in a 75-Year-Old Man

A and B, Shown are hyperintensities involving the temporal lobes bilaterally (A) and the left frontal lobe and parieto-occipital lobe (B). A brain biopsy specimen demonstrated cerebral amyloid angiopathy (CAA), without evidence of inflammation. The patient began a high-dose, 5-day course of intravenous corticosteroids. C and D, One and a half months after the initial presentation, significant resolution of edema and white matter hyperintensities is seen.

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