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Lancet Neurol. 2018 Mar;17(3):232-240. doi: 10.1016/S1474-4422(18)30006-1. Epub 2018 Jan 10.

The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study.

Author information

1
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK.
2
Department of Neurology, Altnagelvin Hospital, Londonderry, UK.
3
Institute of Neuroscience and Institute for Ageing, Newcastle University, Newcastle-upon-Tyne, UK; Newcastle upon Tyne Hospitals National Health Services Foundation Trust, Newcastle-upon-Tyne, UK.
4
Clinical Neurosciences, Clinical and Experimental Sciences, University of Southampton, Southampton, UK.
5
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK; Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, UK.
6
Université Lille, Inserm U1171, Degenerative and Vascular Cognitive Disorders, CHU Lille, Department of Neurology, Lille, France.
7
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK; UK Dementia Research Institute at The University of Edinburgh, The University of Edinburgh, Edinburgh, UK; Row Fogo Centre for Research into Ageing and the Brain, The University of Edinburgh, Edinburgh, UK.
8
Centre for Clinical Brain Sciences, The University of Edinburgh, Edinburgh, UK. Electronic address: rustam.al-shahi@ed.ac.uk.

Abstract

BACKGROUND:

Identification 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.

METHODS:

We 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.

FINDINGS:

Among 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).

INTERPRETATION:

The 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.

FUNDING:

UK Medical Research Council, The Stroke Association, and The Wellcome Trust.

Comment in

PMID:
29331631
PMCID:
PMC5818029
DOI:
10.1016/S1474-4422(18)30006-1
[Indexed for MEDLINE]
Free PMC Article

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