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Published on: March 7, 2019
Spontaneous ARIA-like Events in Cerebral Amyloid Angiopathy-Related Inflammation: A Multicenter Prospective
Laura Antolini1, Jacopo C DiFrancesco1, Marialuisa Zedde1
1From the School of Medicine and Surgery (L.A., J.C.D., G.B., C.F., N.Z., F. Piazza), University of Milano-Bicocca, Monza; Neurology Unit (M.Z.), Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia; IRCCS Fondazione Ca Granda Ospedale Maggiore Policlinico Milano and University of Milan (A.A., E.S.), Italy; Kyoto University Graduate School of Medicine (A.S.), Japan; University of Padova (A.C.); University of Chieti (M. Caulo), Italy; University of Southampton (R.O.C.), UK; Department of Neurology (A.C.), Boston Medical Center, Boston University, MA; University of Campania "Luigi Vanvitelli" (M. Cirillo), Napoli; Università Campus Biomedico (V.D.L.), Rome; Azienda Socio Sanitaria Territoriale di Cremona (A.G.); Italian National Research Council (D.I.), University of Florence; Neuroscience Institute (D.I.), Pisa; S. Bortolo Hospital (M.M., F. Perini), Vicenza; Azienda USL Toscana sud est (R.M.), Grosseto, Italy; National Cerebral and Cardiovascular Center (M.I.), Osaka, Japan; University of São Paulo Medical School (R.N.), Brazil; S.S. Filippo and Nicola Hospital (B.O.), Avezzano; University of Brescia (A.P.); Neuroradiology Unit (R.P.), Azienda Unità Sanitaria Locale-IRCCS di Reggio Emilia; IRCCS Mondino Foundation and University of Pavia (G.P.); Ospedale Papa Giovanni XXIII (M.S.), Bergamo; Fondazione IRCCS "Carlo Besta" National Neurological Institute (F.T.), Milan, Italy; Azienda USL Toscana Centro (R.V.), Prato, Italy; Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER) (J.F.V.-C.), Valencia; Hospital Universitario 12 de Octubre (A.V.-G.), Madrid, Spain; St. Marianna University School of Medicine (Y.H.), Kawasaki, Japan; and CAA and AD Translational Research and Biomarkers Laboratory (F. Piazza), PhD Program in Neuroscience, School of Medicine and Surgery, University of Milano-Bicocca, Monza, Italy.
Background And Objectives:
The goal of this work was to investigate the natural history and outcomes after treatment for spontaneous amyloid-related imaging abnormalities (ARIA)-like in cerebral amyloid angiopathy-related inflammation (CAA-ri).
Methods:
This was a multicenter, hospital-based, longitudinal, prospective observational study of inpatients meeting CAA-ri diagnostic criteria recruited through the Inflammatory Cerebral Amyloid Angiopathy and Alzheimer's Disease βiomarkers International Network from January 2013 to March 2017. A protocol for systematic data collection at first-ever presentation and at subsequent in-person visits, including T1-weighted, gradient recalled echo-T2*, fluid-suppressed T2-weighted (fluid-attenuated inversion recovery), and T1 postgadolinium contrast-enhanced images acquired on 1.5T MRI, was used at the 3-, 6-, 12-, and 24-month follow-up. Centralized reads of MRIs were performed by investigators blinded to clinical, therapeutic, and time-point information. Main outcomes were survival, clinical and radiologic recovery, intracerebral hemorrhage (ICH), and recurrence of CAA-ri.
Results:
The study enrolled 113 participants (10.6% definite, 71.7% probable, and 17.7% possible CAA-ri). Their mean age was 72.9 years; 43.4% were female; 37.1% were APOEε4 carriers; 36.3% had a history of Alzheimer disease; and 33.6% had a history of ICH. A history of ICH and the occurrence of new ICH at follow-up were more common in patients with cortical superficial siderosis at baseline (52.6% vs 14.3%, p < 0.0001 and 19.3% vs 3.6%, p < 0.009, respectively). After the first-ever presentation of CAA-ri, 70.3% (95% confidence interval [CI] 61.6%-78.5%) and 84.1% (95% CI 76.2%-90.6%) clinically recovered within 3 and 12 months, followed by radiologic recovery in 45.1% (95% CI 36.4%-54.8%) and 77.4% (95% CI 67.7%-85.9%), respectively. After clinicoradiologic resolution of the first-ever episode, 38.3% (95% CI 22.9%-59.2%) had at least 1 recurrence within the following 24 months. Recurrence was more likely if IV high-dose corticosteroid pulse therapy was suddenly stopped compared to slow oral tapering off (hazard ratio 4.68, 95% CI 1.57-13.93; p = 0.006).
Discussion:
These results from the largest longitudinal cohort registry of patients with CAA-ri support the transient and potentially relapsing inflammatory nature of the clinical-radiologic acute manifestations of the disease and the effectiveness of slow oral tapering off after IV corticosteroid pulse therapy in preventing recurrences. Our results highlight the importance of differential diagnosis for spontaneous ARIA-like events in β-amyloid-driven diseases, including treatment-related ARIA in patients with Alzheimer disease exposed to immunotherapy drugs.
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