Recurrence of Cerebral Amyloid Angiopathy-Related Inflammation: A Report of Two Cases from the iCAβ International Network

Article type: Research Article

Authors: DiFrancesco, Jacopo C.^{a; b} | Touat, Mehdi^{c; d} | Caulo, Massimo^e | Gallucci, Massimo^f | Garcin, Béatrice^{c; g} | Levy, Richard^{c; g} | Uncini, Antonino^e | Piazza, Fabrizio^{a; h; i; *}

Affiliations: [a] Department of Surgery and Translational Medicine, Milan Center for Neuroscience (NeuroMi), University of Milano-Bicocca, Monza, Italy | [b] Department of Neurology, San Gerardo Hospital, Monza, Italy | [c] Neurology Department, Hospital Saint Antoine, APHP, Paris, France | [d] INSERM UMR 981, Predictive Biomarkers and New Therapeutic Strategies in Oncology, Gustave Roussy, Villejuif, France | [e] Department of Neuroscience and Imaging, University “G. d’Annunzio”, Chieti, Italy | [f] Department on Neuroradiology, University of L’Aquila, L’Aquila, Italy | [g] INSERM UMRS, CNRS UMR, Brain & Spine Institute (ICM), Hôpital Pitié Salpêtrière, Paris, France | [h] The inflammatory Cerebral amyloid angiopathy and Alzheimer’s disease βiomarkers (iCAβ) International Network, Monza, Italy | [i] The iCAβ-ITALY Study Group of the Italian Society for the study of Dementia (SINdem), Italy

Correspondence: [*] Correspondence to: Fabrizio Piazza, PhD, Department of Surgery and Translational Medicine, University of Milano-Bicocca, Via Cadore 48, 20900 Monza, Italy. Tel.: +39 02.6448.8127;Fax: +39 02.6448.8108; [email protected]

Abstract: Background: Cerebral amyloid angiopathy-related inflammation (CAA-ri) represents the most readily responsive form of CAA, if diagnosed and treated early. Although CAA-ri typically presents with a monophasic pattern, recurrences have been occasionally reported. Objectives: To describe the evolution of the clinical and neuroradiological features of CAA-ri recurrence. Methods: From the 60 CAA-ri cases recruited through the iCAβ International Network, we identified those patients who experienced a CAA-ri recurrence at more than 12 months after the first inflammatory event. Neuroradiological evidence of cerebral inflammation (vasogenic edema) and sulcal superficial siderosis or multiple areas of cortical/subcortical microhemorrhages (MHs) were evaluated based upon fluid-attenuated inversion recovery and T2 *-weighted gradient echo or susceptibility weighted imaging, respectively. In one patient, the deposition of amyloid-β was evaluated using 11C-Pittsburgh Compound B-positron emission tomography (PiB-PET). Results: Of the 60 cases, two were identified as having experienced a late CAA-ri recurrence, at two and seven years after the first presentation, respectively. At recurrence, the inflammatory lesions colocalized with the appearance of new MHs and were observed in brain areas different from those where the first onset occurred. PiB-PET four months after remission showed particularly low amyloid-β deposition in the left frontal lobe, while no change was observed in the area of the inflammatory relapse. Conclusions: Our observations highlight the importance of not underestimating any new neurological symptoms in patients who have already experienced an episode of CAA-ri. Although the frequency of CAA-ri recurrences is rare, in cases of suspected relapse, a prompt clinical and radiological follow-up should be considered in order to obtain a timely diagnosis and treatment, having a potential strong impact on patients’ clinical outcome.

Keywords: Alzheimer’s disease, amyloid-PET, amyloid-related imaging abnormalities, cerebral amyloid angiopathy related inflammation, immunotherapy trials, iCAβ International Network, inflammatory relapse, microhemorrhages, steroid treatment, vasogenic edema

DOI: 10.3233/JAD-150070

Journal: Journal of Alzheimer's Disease, vol. 46, no. 4, pp. 1071-1077, 2015