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

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

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.

Journal Article
1474-4422
Rodrigues, Mark A.
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Samarasekera, Neshika
188fa3ee-f39b-442b-992a-52a9279f12fa
Lerpiniere, Christine
349b5e98-1625-4da0-a158-623f8e5787a7
Humphreys, Catherine
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McCarron, Mark O.
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White, Philip M.
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Nicoll, James A.R.
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Sudlow, Cathie L.M.
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Cordonnier, Charlotte
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Wardlaw, Joanna M.
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Smith, Colin
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Al-Shahi Salman, Rustam
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Rodrigues, Mark A.
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Samarasekera, Neshika
188fa3ee-f39b-442b-992a-52a9279f12fa
Lerpiniere, Christine
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Humphreys, Catherine
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McCarron, Mark O.
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White, Philip M.
1249a5ab-d28a-4817-970b-009f73053354
Nicoll, James A.R.
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Sudlow, Cathie L.M.
5939eef1-b204-4db2-af43-c86ab3388acb
Cordonnier, Charlotte
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Wardlaw, Joanna M.
8e7202ad-0fd9-430c-b26a-05b1106ecaad
Smith, Colin
d991039c-1c8b-4aff-a306-b45c67c486e9
Al-Shahi Salman, Rustam
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Rodrigues, Mark A., Samarasekera, Neshika, Lerpiniere, Christine, Humphreys, Catherine, McCarron, Mark O., White, Philip M., Nicoll, James A.R., Sudlow, Cathie L.M., Cordonnier, Charlotte, Wardlaw, Joanna M., Smith, Colin and Al-Shahi Salman, Rustam (2018) The Edinburgh CT and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development and diagnostic test accuracy study. Lancet Neurology. (doi:10.1016/S1474-4422(18)30006-1).

Record type: Article

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.

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Accepted/In Press date: 20 November 2017
e-pub ahead of print date: 10 January 2018
Additional Information: 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.
Keywords: Journal Article

Identifiers

Local EPrints ID: 417092
URI: https://eprints.soton.ac.uk/id/eprint/417092
ISSN: 1474-4422
PURE UUID: 6a696c03-8e5d-411d-91bf-c9d1a4882c26
ORCID for James A.R. Nicoll: ORCID iD orcid.org/0000-0002-9444-7246

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Date deposited: 19 Jan 2018 17:30
Last modified: 11 May 2018 16:31

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Contributors

Author: Mark A. Rodrigues
Author: Neshika Samarasekera
Author: Christine Lerpiniere
Author: Catherine Humphreys
Author: Mark O. McCarron
Author: Philip M. White
Author: Cathie L.M. Sudlow
Author: Charlotte Cordonnier
Author: Joanna M. Wardlaw
Author: Colin Smith
Author: Rustam Al-Shahi Salman

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