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What are the clinical, neuroimaging, laboratory, pathologic, or treatment-related associations with outcomes after an episode of cerebral amyloid angiopathy–related inflammation?
In this cohort study of 48 patients with cerebral amyloid angiopathy–related inflammation, both clinical improvement and radiographic improvement were more likely to occur in individuals treated with an immunosuppressive agent than in untreated individuals; recurrence was also significantly less likely among individuals who received treatment than those who did not. When controlling for treatment, no other variables were associated with outcomes aside from an association between APOE ɛ4 and radiographic improvement.
Early immunosuppressive treatment may improve the disease course of cerebral amyloid angiopathy–related inflammation and reduce the likelihood of recurrence.
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.
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.
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.
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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Accepted for Publication: March 20, 2020.
Corresponding Author: Steven M. Greenberg, MD, PhD, J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, 55 Fruit St, Boston, MA 02114 (email@example.com).
Published Online: June 22, 2020. doi:10.1001/jamaneurol.2020.1782
Author Contributions: Drs Regenhardt and J. M. Thon had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Drs Regenhardt and J. M. Thon contributed equally to this work.
Concept and design: Regenhardt, J. M. Thon, Das, O. R. Thon, Charidimou, Frosch, Cho, Greenberg.
Acquisition, analysis, or interpretation of data: Regenhardt, J. M. Thon, Das, O. R. Thon, Viswanathan, Gurol, Chwalisz, Cho.
Drafting of the manuscript: Regenhardt, J. M. Thon, O. R. Thon, Greenberg.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Regenhardt, J. M. Thon, Das, O. R. Thon.
Obtained funding: Regenhardt, Viswanathan, Frosch.
Administrative, technical, or material support: J. M. Thon, O. R. Thon.
Supervision: Viswanathan, Chwalisz, Frosch, Cho, Greenberg.
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.
Funding/Support: Funding was provided by grant R25 NS065743 from the National Institute of Neurological Disorders and Stroke (Dr Regenhardt) and grant R01 AG026484 from the National Institute of Neurological Disorders and Stroke (Dr Greenberg).
Role of the Funder/Sponsor: The funding source had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
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