Background: Spontaneous intracerebral haemorrhage (ICH) is usually diagnosed by computed tomography (CT). Case series have described CT features of lobar ICH accompanied by cerebral amyloid angiopathy (CAA) on pathological examination. Whether CT features are diagnostic of CAA-associated lobar ICH is unclear.
Methods: We identified adults with first-ever ICH diagnosed by CT in a prospective, population-based inception cohort study, who died and underwent research post-mortem. Two radiologists rated CT imaging appearances using a standardised proforma, blinded to clinical, genetic and histopathological features. We used blood or cerebellar tissue to determine apolipoprotein E (APOE) genotype. A neuropathologist rated brain tissue for small vessel diseases – including CAA, identified by beta-amyloid immunohistochemistry, rated using a standardised scale – masked to clinical, radiographic and genetic features. The primary outcome was CAA-associated lobar ICH (left cerebral hemisphere summed parenchymal CAA score ≥5).
Findings: Among 110 adults (median age 83 years [IQR 76-87], 49 [45%] male), ICH was lobar in 62 (56%), deep in 41 (37%) and infratentorial in seven (6%). Among 62 lobar ICH, 36 (58%) were CAA-associated and they were independently associated with subarachnoid haemorrhage (32/36 [89%] versus 11/26 [42%]; p=0·01), ICH with finger-like projections (14/36 [39%] versus 0/26 [0%]; p=0·04) and APOE ε4+ (18/36 [50%] versus 2/26 [8%]; p=0·002). Diagnostic criteria for CAA-associated lobar ICH using these three variables had excellent discrimination (c-statistic 0.92, 95%CI 0.86-0.98), confirmed by internal validation. The rule-out criteria neither subarachnoid haemorrhage nor APOE ε4+ had 100% sensitivity (95%CI 88-100%). The rule-in criteria subarachnoid haemorrhage and either APOE ε4+ or finger-like projections had 96% specificity (95%CI 78-100%).
Interpretation: Diagnostic criteria based on CT and APOE genotype show excellent discrimination for CAA-associated lobar ICH. These ‘rule-in’ and ‘rule-out’ criteria may might inform prognostic and therapeutic decisions that depend on identifying CAA-associated lobar ICH.
Rodrigues, Mark; Al-Shahi Salman, Rustam. (2017). The Edinburgh Computed tomography and genetic diagnostic criteria for lobar intracerebral haemorrhage associated with cerebral amyloid angiopathy: model development, internal validation and diagnostic test accuracy study, 2010-2016 [dataset]. University of Edinburgh. College of Medicine & Veterinary Medicine. Centre for Clinical Brain Sciences. http://dx.doi.org/10.7488/ds/2230.