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. 2020 Oct 1;77(10):1261-1269.
doi: 10.1001/jamaneurol.2020.1782.

Association Between Immunosuppressive Treatment and Outcomes of Cerebral Amyloid Angiopathy-Related Inflammation

Robert W Regenhardt  1 , Jesse M Thon  1 , Alvin S Das  1 , Olga R Thon  1 , Andreas Charidimou  1 , Anand Viswanathan  1 , M Edip Gurol  1 , Bart K Chwalisz  1 , Matthew P Frosch  2 , Tracey A Cho  3 , Steven M Greenberg  1
Affiliations

Association Between Immunosuppressive Treatment and Outcomes of Cerebral Amyloid Angiopathy-Related Inflammation

Robert W Regenhardt et al. JAMA Neurol. .

Abstract

Importance: Cerebral amyloid angiopathy-related inflammation (CAA-ri), a distinct subtype of cerebral amyloid angiopathy, is characterized by an autoimmune reaction to cerebrovascular β-amyloid deposits. Outcomes and response to immunosuppressive therapy for CAA-ri are poorly understood.

Objective: To identify clinical, neuroimaging, laboratory, pathologic, or treatment-related associations with outcomes after an episode of CAA-ri.

Design, setting, and participants: A retrospective cohort study of prospectively identified individuals who presented from July 3, 1998, to November 27, 2017, with a median follow-up of 2.7 years (interquartile range, 1.0-5.5 years). The study included 48 consecutive patients with CAA-ri meeting diagnostic criteria who had at least 1 disease episode and subsequent outcome data. No patients refused or were excluded.

Exposures: Prespecified candidate variables were immunosuppressive therapies, cerebrospinal fluid pleocytosis, magnetic resonance imaging findings of recent infarcts or contrast enhancement, and histopathologic evidence of vessel wall inflammation.

Main outcomes and measures: Clinical improvement and worsening were defined by persistent changes in signs or symptoms, radiographic improvement by decreased subcortical foci of T2 hyperintensity or T1 enhancement, and radiographic worsening by increased subcortical T2 hyperintensity, T1 enhancement, or infarcts. Disease recurrence was defined as new-onset clinical symptoms associated with new imaging findings.

Results: The 48 individuals in the study included 29 women and had a mean (SD) age of 68.9 (9.9) years. Results of presenting magnetic resonance imaging revealed that 10 of 29 patients with CAA-ri (34%) had T1 contrast enhancement, 30 of 32 (94%) had subcortical T2 hyperintensity (22 of 30 [73%] asymmetric), 7 of 32 (22%) had acute or subacute punctate infarcts, and 27 of 31 (87%) had microbleeds. Immunosuppressive treatments after first episodes included corticosteroids (33 [69%]), cyclophosphamide (6 [13%]), and mycophenolate (2 [4%]); 14 patients (29%) received no treatment. Clinical improvement and radiographic improvement were each more likely in individuals treated with an immunosuppressive agent than with no treatment (clinical improvement: 32 of 34 [94%] vs 7 of 14 [50%]; odds ratio, 16.0; 95% CI, 2.72-94.1; radiographic improvement: 24 of 28 [86%] vs 4 of 14 [29%]; odds ratio, 15.0; 95% CI, 3.12-72.1). Recurrence was less likely if CAA-ri was treated with any immunosuppressant agent than not (9 of 34 [26%] vs 10 of 14 [71%]; hazard ratio, 0.19; 95% CI, 0.07-0.48). When controlling for treatment, no variables were associated with outcomes aside from an association between APOE ɛ4 and radiographic improvement (odds ratio, 4.49; 95% CI, 1.11-18.2).

Conclusions and relevance: These results from a relatively large series of patients with CAA-ri support the effectiveness of immunosuppressive treatment and suggest that early treatment may both improve the initial disease course and reduce the likelihood of recurrence. These results raise the possibility that early blunting of CAA-ri and the autoimmune response may have long-term benefits for the subsequent disease course.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Regenhardt reported receiving grants from the National Institutes of Health–National Institute of Neurological Disorders and Stroke during the conduct of the study. Dr Gurol reported receiving grants from AVID (Eli Lilly), Pfizer, and Boston Scientific outside the submitted work. Dr Greenberg reported receiving grants from the National Institutes of Health during the conduct of the study. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Magnetic Resonance Imaging Findings of Cerebral Amyloid Angiopathy–Related Inflammation
Magnetic resonance imaging images are shown for a 79-year-old woman who presented with seizure. A, Fluid-attenuated inversion recovery (FLAIR) images show right-sided asymmetric subcortical regions of hyperintensity suggestive of subcortical edema. B, Postcontrast T1-weighted images show right-sided, primarily leptomeningeal contrast enhancement. C, The same right-sided predilection was also noted for foci of cortical superficial siderosis and microbleeds seen on susceptibility-weighted imaging (SWI) images.
Figure 2.
Figure 2.. Time to Recurrence Comparing Any Immunosuppressive Therapy With No Immunosuppressive Therapy After First Episode of Cerebral Amyloid Angiopathy–Related Inflammation
HR indicates hazard ratio.
See this image and copyright information in PMC

References

    1. Eng JA, Frosch MP, Choi K, Rebeck GW, Greenberg SM. Clinical manifestations of cerebral amyloid angiopathy–related inflammation. Ann Neurol. 2004;55(2):250-256. doi:10.1002/ana.10810 - DOI - PubMed
    1. Oh U, Gupta R, Krakauer JW, Khandji AG, Chin SS, Elkind MSV. Reversible leukoencephalopathy associated with cerebral amyloid angiopathy. Neurology. 2004;62(3):494-497. doi:10.1212/01.WNL.0000106951.94624.DF - DOI - PubMed
    1. Piazza F, Greenberg SM, Savoiardo M, et al. . Anti-amyloid β autoantibodies in cerebral amyloid angiopathy–related inflammation: implications for amyloid-modifying therapies. Ann Neurol. 2013;73(4):449-458. doi:10.1002/ana.23857 - DOI - PubMed
    1. Kimura A, Sakurai T, Yoshikura N, et al. . Corticosteroid therapy in a patient with cerebral amyloid angiopathy–related inflammation. J Neuroinflammation. 2013;10:39. doi:10.1186/1742-2094-10-39 - DOI - PMC - PubMed
    1. Fountain NB, Eberhard DA. Primary angiitis of the central nervous system associated with cerebral amyloid angiopathy: report of two cases and review of the literature. Neurology. 1996;46(1):190-197. doi:10.1212/WNL.46.1.190 - DOI - PubMed

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