Identifying diagnostic and prognostic factors in cerebral amyloid angiopathy‐related inflammation: a systematic analysis of published and seven new cases

Abstract Aims Cerebral amyloid angiopathy‐related inflammation (CAA‐RI) is a potentially reversible manifestation of CAA, histopathologically characterised by transmural and/or perivascular inflammatory infiltrates. We aimed to identify clinical, radiological, and laboratory variables capable of improving or supporting the diagnosis of or predicting/influencing the prognosis of CAA‐RI and to retrospectively evaluate different therapeutic approaches. Methods We present clinical and neuroradiological observations in seven unpublished CAA‐RI cases, including neuropathological findings in two definite cases. These cases were included in a systematic analysis of probable/definite CAA‐RI cases published in the literature up to December 31, 2021. Descriptive and associative analyses were performed, including a set of clinical, radiological, and laboratory variables to predict short‐term, 6‐month, and 1‐year outcomes and mortality, first on definite, secondly on an expanded probable/definite CAA‐RI cohort. Results Data on 205 definite and 100 probable cases were analysed. CAA‐RI had a younger symptomatic onset than non‐inflammatory CAA, without sex preference. Transmural histology was more likely to be associated with the co‐localisation of microbleeds with confluent white matter hyperintensities on MRI. Incorporating leptomeningeal enhancement and/or sulcal non‐nulling on fluid‐attenuated inversion recovery (FLAIR) enhanced the sensitivity of the criteria. Cerebrospinal fluid pleocytosis was associated with a decreased probability of clinical improvement and longer‐term positive outcomes. Future lobar haemorrhage was associated with adverse outcomes, including mortality. Immunosuppression was associated with short‐term improvement, with less clear effects on long‐term outcomes. The superiority of high‐dose over low‐dose corticosteroids was not established. Conclusions This is the largest retrospective associative analysis of published CAA‐RI cases, and the first to include an expanded probable/definite cohort to identify diagnostic/prognostic markers. We propose points for further crystallisation of the criteria and directions for future prospective studies.