Cerebral Amyloid Angiopathy and Cerebral Amyloid Angiopathy-Related Inflammation: Comparison of Hemorrhagic and DWI MRI Features

Article type: Research Article

Authors: Renard, Dimitri^{a; *} | Tatu, Lavinia^a | Collombier, Laurent^b | Wacongne, Anne^a | Ayrignac, Xavier^c | Charif, Mahmoud^c | Boukriche, Yassine^d | Chiper, Laura^d | Fourcade, Genevieve^e | Azakri, Souhayla^c | Gaillard, Nicolas^f | Mercier, Erick^g | Lehmann, Sylvain^h | Thouvenot, Eric^{a; i}

Affiliations: [a] Department of Neurology, Nîmes University Hospital, Nîmes, France | [b] Department of Nuclear Medicine, Nîmes University Hospital, Nîmes, France | [c] Department of Neurology, Montpellier University Hospital, Montpellier, France | [d] Department of Neurology, CH Beziers, France | [e] Department of Neurology, CH Narbonne, France | [f] Department of Neurology, CH Perpignan, France | [g] Department of Hematology, Nîmes University Hospital, Nîmes, France | [h] Laboratoire de Biochimie-Protéomique Clinique – IRMB – CRB - Inserm U11183, CHU Montpellier, Hôpital St-Eloi - Université Montpellier, France | [i] Institut de Génomique Fonctionnelle, UMR5203, Université Montpellier, Montpellier, France

Correspondence: [*] Correspondence to: Dimitri Renard, MD, Department of Neurology, CHU Nîmes, Hôpital Caremeau, 4, Rue du Pr Debré, 30029 Nîmes Cedex 4, France. Tel.: +33 4 66 68 32 61; Fax: +33 4 66 68 40 16; E-mail: [email protected].

Abstract: Background:Cerebral amyloid angiopathy (CAA) can be associated with primary vasculitis of small/medium-sized leptomeningeal and cortical arteries, called CAA-related inflammation (CAA-ri). Objective:To compare hemorrhagic and diffusion-weighted imaging (DWI) MRI features in CAA and CAA-ri. Methods:We prospectively scored in a consecutive CAA and CAA-ri cohort: presence/number of chronic intracerebral hemorrhage (ICH), cerebral microbleeds (CMB), and cortical superficial siderosis (CSS) on initial T2*-weighted imaging, and DWI lesions on both initial and follow-up imaging. In a subgroup, ApoE, CSF, and 18F-florbetaben-positron emission tomography (FBB-PET) were also analyzed. Results:In CAA-ri, CMB presence was more frequent (100% versus 40%, p < 0.001) and CMB numbers higher (mean 137 versus 8, p < 0.001). No difference was observed for chronic ICH or CSS. DWI lesions were more frequent in acute compared to chronic CAA-ri (p = 0.025), whereas no such difference was observed between acute and chronic CAA (p = 0.18). Both ApoE4 (genotyping available in 22 CAA-ri and 48 CAA patients) carriers and homozygosity were more frequent in CAA-ri (48% versus 19% [p = 0.014] and 32% versus 2% [p < 0.001] respectively). CSF biomarker analyses (performed in 20 CAA-ri and 45 CAA patients) showed lower Aβ42 levels in CAA-ri compared to CAA (median 312 versus 422 pg/mL, p = 0.0032). FBB-PET (performed in 11 CAA-ri and 20 CAA patients) showed higher standardized uptake value ratios in CAA-ri compared with CAA, only significant when the pons was used as reference (p = 0.037). Conclusion:Compared to CAA, CAA-ri was associated with higher CMB numbers, more frequent ApoE4 carriers and homozygotes, lower CSF Aβ42 levels, and more severe amyloid load on FBB-PET.

Keywords: Amyloid imaging, apolipoprotein E genotype, cerebral amyloid angiopathy, cerebral amyloid angiopathy-related inflammation, cerebral microbleeds, cerebrospinal fluid, florbetaben, intracerebral hemorrhage, positron emission tomography

DOI: 10.3233/JAD-180269

Journal: Journal of Alzheimer's Disease, vol. 64, no. 4, pp. 1113-1121, 2018