Journal article
Association Between Immunosuppressive Treatment and Outcomes of Cerebral Amyloid Angiopathy-Related Inflammation
JAMA neurology, Vol.77(10), pp.1261-1269
10/01/2020
DOI: 10.1001/jamaneurol.2020.1782
PMCID: PMC7309570
PMID: 32568365
Abstract
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.
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.
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).
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.
Details
- Title: Subtitle
- Association Between Immunosuppressive Treatment and Outcomes of Cerebral Amyloid Angiopathy-Related Inflammation
- Creators
- Robert W Regenhardt - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, BostonJesse M Thon - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, BostonAlvin S Das - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, BostonOlga R Thon - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, BostonAndreas Charidimou - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, BostonAnand Viswanathan - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, BostonM Edip Gurol - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, BostonBart K Chwalisz - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, BostonMatthew P Frosch - Neuropathology Service, C. S. Kubik Laboratory for Neuropathology, Massachusetts General Hospital, Harvard Medical School, BostonTracey A Cho - Department of Neurology, University of Iowa Hospitals and Clinics, Iowa CitySteven M Greenberg - J. Philip Kistler Stroke Research Center, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston
- Resource Type
- Journal article
- Publication Details
- JAMA neurology, Vol.77(10), pp.1261-1269
- DOI
- 10.1001/jamaneurol.2020.1782
- PMID
- 32568365
- PMCID
- PMC7309570
- NLM abbreviation
- JAMA Neurol
- ISSN
- 2168-6149
- eISSN
- 2168-6157
- Publisher
- United States
- Grant note
- R25 NS065743 / NINDS NIH HHS
- Language
- English
- Date published
- 10/01/2020
- Academic Unit
- Neurology; Iowa Neuroscience Institute
- Record Identifier
- 9984070404102771
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