Elsevier

The Lancet Neurology

Volume 11, Issue 4, April 2012, Pages 307-314
The Lancet Neurology

Articles
Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study

https://doi.org/10.1016/S1474-4422(12)70038-8Get rights and content

Summary

Background

In patients with intracerebral haemorrhage (ICH), early haemorrhage expansion affects clinical outcome. Haemostatic treatment reduces haematoma expansion, but fails to improve clinical outcomes in many patients. Proper selection of patients at high risk for haematoma expansion seems crucial to improve outcomes. In this study, we aimed to prospectively validate the CT-angiography (CTA) spot sign for prediction of haematoma expansion.

Methods

PREDICT (predicting haematoma growth and outcome in intracerebral haemorrhage using contrast bolus CT) was a multicentre prospective observational cohort study. We recruited patients aged 18 years or older, with ICH smaller than 100 mL, and presenting at less than 6 h from symptom onset. Using two independent core laboratories, one neuroradiologist determined CTA spot-sign status, whereas another neurologist masked for clinical outcomes and imaging measured haematoma volumes by computerised planimetry. The primary outcome was haematoma expansion defined as absolute growth greater than 6 mL or a relative growth of more than 33% from initial CT to follow-up CT. We reported data using standard descriptive statistics stratified by the CTA spot sign. Mortality was assessed with Kaplan-Meier survival analysis.

Findings

We enrolled 268 patients. Median time from symptom onset to baseline CT was 135 min (range 22–470), and time from onset to CTA was 159 min (32–475). 81 (30%) patients were spot-sign positive. The primary analysis included 228 patients, who had a follow-up CT before surgery or death. Median baseline ICH volume was 19·9 mL (1·5–80·9) in spot-sign-positive patients versus 10·0 mL (0·1–102·7) in spot-sign negative patients (p<0·001). Median ICH expansion was 8·6 mL (−9·3 to 121·7) for spot-sign positive patients and 0·4 mL (−11·7 to 98·3) for spot-negative patients (p<0·001). In those with haematoma expansion, the positive predictive value for the spot sign was 61% (95% CI 47–73); the negative predictive value was 78% (71–84), sensitivity was 51% (39–63), and specificity was 85% (78–90). Median 3-month modified Rankin Scale (mRS) was 5 in CTA spot-sign-positive patients, and 3 in spot-sign-negative patients (p<0·001). Mortality at 3 months was 43·4% (23 of 53) in CTA spot-sign positive versus 19·6% (31 of 158) in CTA spot-sign-negative patients (HR 2·4, 95% CI 1·4–4·0, p=0·002).

Interpretation

These findings confirm previous single-centre studies showing that the CTA spot sign is a predictor of haematoma expansion. The spot sign is recommended as an entry criterion for future trials of haemostatic therapy in patients with acute ICH.

Funding

Canadian Stroke Consortium and NovoNordisk Canada.

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

References (30)

  • YH Wang et al.

    Hematoma volume affects the accuracy of computed tomographic angiography ‘spot sign’ in predicting hematoma expansion after acute intracerebral hemorrhage

    Eur Neurol

    (2011)
  • JP Broderick et al.

    Intracerebral hemorrhage more than twice as common as subarachnoid hemorrhage

    J Neurosurg

    (1993)
  • JC Hemphill et al.

    The ICH score: a simple, reliable grading scale for intracerebral hemorrhage

    Stroke

    (2001)
  • R Leira et al.

    Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors

    Neurology

    (2004)
  • T Brott et al.

    Early hemorrhage growth in patients with intracerebral hemorrhage

    Stroke

    (1997)
  • SM Davis et al.

    Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage

    Neurology

    (2006)
  • SA Mayer et al.

    Recombinant activated factor VII for acute intracerebral hemorrhage

    N Engl J Med

    (2005)
  • SA Mayer et al.

    Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage

    N Engl J Med

    (2008)
  • SA Mayer et al.

    Can a subset of intracerebral hemorrhage patients benefit from hemostatic therapy with recombinant activated factor VII?

    Stroke

    (2009)
  • R Wada et al.

    CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage

    Stroke

    (2007)
  • JN Goldstein et al.

    Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage

    Neurology

    (2007)
  • J Kim et al.

    Contrast extravasation on CT predicts mortality in primary intracerebral hemorrhage

    AJNR Am J Neuroradiol

    (2008)
  • N Li et al.

    Contrast extravasation on computed tomography angiography predicts clinical outcome in primary intracerebral hemorrhage: a prospective study of 139 cases

    Stroke

    (2011)
  • SY Park et al.

    Role of ‘spot sign’ on CT angiography to predict hematoma expansion in spontaneous intracerebral hemorrhage

    J Korean Neurosurg Soc

    (2010)
  • JE Delgado Almandoz et al.

    Systematic characterization of the computed tomography angiography spot sign in primary intracerebral hemorrhage identifies patients at highest risk for hematoma expansion: the spot sign score

    Stroke

    (2009)
  • Cited by (495)

    • Current Evaluation of Intracerebral Hemorrhage

      2023, Radiologic Clinics of North America
    View all citing articles on Scopus
    View full text