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

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METHODS: We present clinical and neuroradiological observations in seven unpublished CAA-RI cases, including neuropathological findings in two definite cases.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.