ArticlesPrediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study
Introduction
Intracerebral haemorrhage (ICH) accounts for about 7–15% of all strokes and carries a mortality rate of about 40%, with half of the fatalities occurring within the first 2 days after an ictus.1 The most important predictors of outcome after ICH are volume of ICH, Glasgow coma scale (GCS) score, presence of intraventricular blood, and age.2 Haematoma expansion is common, usually occurs in the early phase of ICH, and is strongly associated with poor outcome. Clinically, it manifests as early neurological deterioration,3 often leading to death.4, 5 Given the association of poor outcome with haematoma expansion and final ICH volume, therapeutic intervention aimed at preventing such expansion could represent an acute treatment paradigm for ICH.
Results from trials with haemostatic drugs, such as intravenous recombinant factor VIIa (rFVIIa), have shown reductions in haematoma expansion,6 but have not consistently shown improved clinical outcomes.7 This apparent discrepancy might be due to the inclusion of a majority of patients unlikely to benefit from haemostatic therapy, since only one in three patients with ICH have substantial haematoma expansion within the first few hours.4 Furthermore, patients presenting to hospital with large haematomas will invariably have bad outcomes, with or without subsequent haematoma expansion. Perhaps the clinical efficacy of a haemostatic agent could be optimised by stratifying patients at highest risk of haematoma expansion, and excluding those destined for a poor outcome irrespective of therapy.8
A marker predictive of haematoma expansion could aid the selection of patients for haemostatic treatment, especially in patients presenting with small-to-moderate ICH volumes. One such important surrogate for identification of continued bleeding is contrast extravasation seen on CTA. The CTA spot sign refers to one or more foci of contrast enhancement within an acute primary parenchymal haematoma visible on the source images of CTA. Data from several single-centre studies9, 10, 11, 12, 13, 14 show that the CTA spot sign is a marker of increased risk of haemorrhage growth. The CTA spot sign occurs in about a third of patients scanned within 3 h, and on the basis of data from the single-centre studies, the predictive value for substantial haematoma expansion within 3 h is high. Inter-reader reliability was good to very good (kappa ranging from 0·77 to 0·94) among physicians including neuroradiologists, fellows, and emergency doctors.9, 10, 12, 15 Specificity and positive predictive value (PPV) decline with increasing time from onset, but negative predictive value (NPV) remains unchanged. Recently, a spot-sign score was developed on the basis of single-centre data, and it was predictive of extent of haematoma expansion15 and clinical outcome.16
The primary aim of the predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT (PREDICT) study was to validate previous single-centre observations in a prospective multicentre study with blinded evaluation of haematoma volume and CTA spot-sign interpretation. We sought to establish the sensitivity, specificity, and predictive values of the CTA spot sign for predicting haematoma expansion and clinical outcome.
Section snippets
Patients
PREDICT was a multicentre, prospective, observational cohort study of patients aged 18 years or older who presented with an acute symptomatic and radiologically confirmed ICH. Patients were eligible for entry if they presented within 6 h of onset with a primary or anticoagulant-associated ICH of less than 100 mL (estimated using ABC/2 methods).17, 18 Exclusion criteria included known renal impairment that precluded CTA, premorbid dependence defined as modified Rankin scale (mRS) score greater
Results
268 patients were enrolled in 12 centres in six countries from June 24, 2006, to Sept 6, 2010. No adverse events were reported directly attributable to the CT angiogram. 40 patients were excluded from the primary analysis for the following reasons: 14 were treated with rFVIIa before follow-up CT; 15 were treated with surgical evacuation before follow-up CT; seven died before follow-up CT, and four did not have a follow-up CT for unknown reasons. The excluded population had a high spot-sign
Discussion
This prospective multicentre study confirms the association between the CTA spot sign and haematoma expansion. The CTA spot sign is highly predictive of haematoma expansion irrespective of haematoma expansion definition and for both intraparenchymal and intraventricular haemorrhage growth. The CTA spot sign is associated with a poor prognosis, high rates of early clinical deterioration, and mortality, often occurring within days after onset. The spot sign is also associated with larger
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