• Mark A Rodrigues, Neshika Samarasekera, Christine Lerpiniere, Catherine Humphreys, Mark O McCarron, Philip M White, NicollJames A RJARClinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK., SudlowCathie L MCLMCentre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK; Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK., Charlotte Cordonnier, Joanna M Wardlaw, Colin Smith, and Rustam Al-Shahi Salman.
• Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.
• Lancet Neurol. 2018 Mar 1; 17 (3): 232240232-240.

BackgroundIdentification of lobar spontaneous intracerebral haemorrhage associated with cerebral amyloid angiopathy (CAA) is important because it is associated with a higher risk of recurrent intracerebral haemorrhage than arteriolosclerosis-associated intracerebral haemorrhage. We aimed to develop a prediction model for the identification of CAA-associated lobar intracerebral haemorrhage using CT features and genotype.MethodsWe identified adults with first-ever intracerebral haemorrhage diagnosed by CT, who died and underwent research autopsy as part of the Lothian IntraCerebral Haemorrhage, Pathology, Imaging and Neurological Outcome (LINCHPIN) study, a prospective, population-based, inception cohort. We determined APOE genotype and radiologists rated CT imaging appearances. Radiologists were not aware of clinical, genetic, and histopathological features. A neuropathologist rated brain tissue for small vessel diseases, including CAA, and was masked to clinical, radiographic, and genetic features. We used CT and APOE genotype data in a logistic regression model, which we internally validated using bootstrapping, to predict the risk of CAA-associated lobar intracerebral haemorrhage, derive diagnostic criteria, and estimate diagnostic accuracy.FindingsAmong 110 adults (median age 83 years [IQR 76-87], 49 [45%] men) included in the LINCHPIN study between June 1, 2010 and Feb 10, 2016, intracerebral haemorrhage was lobar in 62 (56%) participants, deep in 41 (37%), and infratentorial in seven (6%). Of the 62 participants with lobar intracerebral haemorrhage, 36 (58%) were associated with moderate or severe CAA compared with 26 (42%) that were associated with absent or mild CAA, and were independently associated with subarachnoid haemorrhage (32 [89%] of 36 vs 11 [42%] of 26; p=0·014), intracerebral haemorrhage with finger-like projections (14 [39%] of 36 vs 0; p=0·043), and APOE ɛ4 possession (18 [50%] of 36 vs 2 [8%] of 26; p=0·0020). A prediction model for CAA-associated lobar intracerebral haemorrhage using these three variables had excellent discrimination (c statistic 0·92, 95% CI 0·86-0·98), confirmed by internal validation. For the rule-out criteria, neither subarachnoid haemorrhage nor APOE ɛ4 possession had 100% sensitivity (95% CI 88-100). For the rule-in criteria, subarachnoid haemorrhage and either APOE ɛ4 possession or finger-like projections had 96% specificity (95% CI 78-100).InterpretationThe CT and APOE genotype prediction model for CAA-associated lobar intracerebral haemorrhage shows excellent discrimination in this cohort, but requires external validation. The Edinburgh rule-in and rule-out diagnostic criteria might inform prognostic and therapeutic decisions that depend on identification of CAA-associated lobar intracerebral haemorrhage.FundingUK Medical Research Council, The Stroke Association, and The Wellcome Trust.Copyright © 2018 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

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