Clinical, biological and neuroradiological evolution of Cerebral Amyloid Angiopathy-related inflammation: the iCAβ International Network longitudinal study.

Background and objective: Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rare and aggressive meningoencephalitis characterized by the acute onset of neurological symptoms associated with radiological evidence of cerebral vasogenic edema (VE) and cortical/subcortical microhemorrhages (MH). Here, we described the clinical, neuroradiological and biological evolution of CAA-ri, to provide future directions for the proper management of this challenging disease. Patients: From the iCAβ International Network, we identified those patients with a follow-up of >12 months. All patients were diagnosed as possible, probable or definitive CAA-ri according to the Auriel 2016 diagnostic criteria. Methods: VE and MHs were evaluated on fluid-attenuated inversion recovery (FLAIR) and T2*-weighted gradient echo (T2*-GRE) or susceptibility weighted imaging (SWI) MRI. CSF autoantibodies, TFPI, Abeta and tau were assessed. Clinical and therapeutic findings recorded. Results: 2/60 patients were identified to undergo CAA-ri recurrence, respectively at two and seven years after first presentation. At recurrence, VE colocalized with the appearance of new MHs, affecting brain areas different from those where the first event occurred. CSF autoantibodies and TFPI revealed as good diagnostic and prognostic biomarkers of VE and MHs, respectively. Conclusions: Our observations improve the understanding of the natural history of CAA-ri, highlighting the importance of a prompt diagnosis, particularly in patients who have already experienced a previous episode of CAA-ri. Although the frequency of late CAA-ri recurrence is rare, in the suspect of relapse, a prompt clinical and radiological follow-up should be considered, to obtain a timely diagnosis and medication with strong impact on the patients’ outcome. References: Piazza F, Greenberg SM, Savoiardo M, et al. Anti-amyloid beta autoantibodies in cerebral amyloid angiopathy related inflammation: implications for amyloid-modifying therapies. Annals of Neurology 2013; 73:449–58. DiFrancesco JC, Longoni M, and Piazza F. Anti-Aβ autoantibodies in amyloid related imaging abnormalities (ARIA): candidate biomarker for immunotherapy in Alzheimer’s disease and cerebral amyloid angiopathy. Front. Neurol. 2015; 25 6:207. Auriel E, Charidimou A, Gurol ME, Ni J, Van Etten ES, Martinez-Ramirez S, Boulouis G, Piazza F, DiFrancesco JC, Frosch MP, Pontes-Neto OV, Shoamanesh A, Reijmer Y, Vashkevich A, Ayres AM, Schwab KM, Viswanathan A, Greenberg S. Validation of Clinicoradiological Criteria for the Diagnosis of Cerebral Amyloid Angiopathy-Related Inflammation. JAMA Neurol. 2016; 73(2):197-202.