Background: A spot sign on computed tomography angiography (CTA) is a potentially strong predictor of poor outcome on ultra-early radiological imaging. The aim of this study was to assess the spot sign as a predictor of functional outcome at 3 months as well as long-term mortality, with a focus on the ability to identify patients with a spontaneous, acceptable outcome. Methods: In a prospective, consecutive single-centre registry of acute stroke patients, we investigated patients with spontaneous intracerebral haemorrhage (ICH) admitted within 4.5 h after symptom onset from April 2009 to January 2013. The standard work-up in our centre included CTA for spot sign status, unless a contraindication was present. Modified Rankin Scale (mRS) scores were assessed at 3 months in the outpatient clinic or by telephone interviews. Long-term mortality was assessed by electronic chart follow-up for up to 1,500 days. Results: Of the 128 patients, 37 (28.9%) had a spot sign on admission CTA. The presence of a spot sign was associated with larger median admission haematoma volume [38.0 ml (IQR 18.0-78.0) vs. 12.0 ml (5.0-24.0); p < 0.0001] and higher median National Institutes of Health Stroke Scale score [19 (IQR 12-23) vs. 12 (6-16); p < 0.0001]. Three months after stroke, the median functional outcome was considerably better in patients without spot sign [mRS score 3 (IQR 2-4) vs. 6 (4-6); p < 0.0001]. The absence of a spot sign showed a sensitivity and specificity for good outcome (mRS scores 0-2) of 0.91 and 0.36, respectively. The presence of a spot sign was, in multivariate models, an independent inverse predictor of good 3-month outcome (OR 0.17; 95% CI: 0.03-0.88) as well as a prominent independent predictor of poor 3-month outcome (mRS scores 5-6; OR 3.40; 95% CI: 1.10-10.5) and death during follow-up (HR 3.04; 95% CI: 1.45-6.34). Patients with a spot sign surviving the acute phase had long-term survival comparable to patients with no spot sign. Conclusion: The absence or presence of a spot sign is a reliable ultra-early predictor of long-term mortality and functional outcome in patients with spontaneous ICH.

Keywords:
Spot sign, Intracerebral haemorrhage, Outcome, Computed tomography angiography
1.
Broderick JP, Brott TG, Duldner JE, Tomsick T, Huster G: Volume of intracerebral hemorrhage: a powerful and easy-to-use predictor of 30-day mortality. Stroke 1993;24:987-993.
2.
Lovelock CE, Molyneux AJ, Rothwell PM: Change in incidence and aetiology of intracerebral haemorrhage in Oxfordshire, UK, between 1981 and 2006: a population-based study. Lancet Neurol 2007;6:487-493.
3.
Counsell C, Boonyakarnkul S, Dennis M, Sandercock P, Bamford J, Burn J, Warlow C: Primary intracerebral haemorrhage in the Oxfordshire Community Stroke Project. Cerebrovasc Dis 1995;5:26-34.
4.
Anderson CS, Heeley E, Huang Y, Wang J, Stapf C, Delcourt C, Lindley R, Robinson T, Lavados P, Neal B, Hata J, Arima H, Parsons M, Li Y, Heritier S, Li Q, Woodward M, Simes RJ, Davis SM, Chalmers J: Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 2013;368:2355-2365.
5.
Mendelow AD, Gregson BA, Rowan EN, Murray GD, Gholkar A, Mitchell PM: Early surgery versus initial conservative treatment in patients with spontaneous supratentorial lobar intracerebral haematomas (STICH II): a randomised trial. Lancet 2013;382:397-408.
6.
Wada R, Aviv RI, Fox AJ, Sahlas DJ, Gladstone DJ, Tomlinson G, Symons SP: CT angiography ‘spot sign' predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 2007;38:1257-1262.
7.
Davis SM, Broderick J, Hennerici M, Brun NC, Diringer MN, Mayer SA, Begtrup K, Steiner T: Hematoma growth is a determinant of mortality and poor outcome after intracerebral hemorrhage. Neurology 2006;66:1175-1181.
8.
Kazui S, Minematsu K, Yamamoto H, Sawada T, Yamaguchi T: Predisposing factors to enlargement of spontaneous intracerebral hematoma. Stroke 1997;28:2370-2375.
9.
Leira R, Davalos A, Silva Y, Gil-Peralta A, Tejada J, Garcia M, Castillo J: Early neurologic deterioration in intracerebral hemorrhage: predictors and associated factors. Neurology 2004;63:461-467.
10.
Brott T, Broderick J, Kothari R, Barsan W, Tomsick T, Sauerbeck L, Spilker J, Duldner J, Khoury J: Early hemorrhage growth in patients with intracerebral hemorrhage. Stroke 1997;28:1-5.
11.
Fujii Y, Takeuchi S, Sasaki O, Minakawa T, Tanaka R: Multivariate analysis of predictors of hematoma enlargement in spontaneous intracerebral hemorrhage. Stroke 1998;29:1160-1166.
12.
Rodriguez-Luna D, Rubiera M, Ribo M, Coscojuela P, Piñeiro S, Pagola J, Hernandez-Guillamon M, Ibarra B, Romero F, Alvarez-Sabin J, Montaner J, Molina CA: Ultraearly hematoma growth predicts poor outcome after acute intracerebral hemorrhage. Neurology 2011;77:1599-1604.
13.
Li N, Wang Y, Wang W, Ma L, Xue J, Weissenborn K, Dengler R, Worthmann H, Wang DZ, Gao P, Liu L, Zhao X: Contrast extravasation on computed tomography angiography predicts clinical outcome in primary intracerebral hemorrhage: a prospective study of 139 cases. Stroke 2011;42:3441-3446.
14.
Rizos T, Dörner N, Jenetzky E, Sykora M, Mundiyanapurath S, Horstmann S, Veltkamp R, Rohde S, Bendszus M, Steiner T: Spot signs in intracerebral hemorrhage: useful for identifying patients at risk for hematoma enlargement? Cerebrovasc Dis 2013;35:582-589.
15.
Wang YH, Fan JY, Luo GD, Lin T, Xie DX, Ji FY, Zhang XT: Hematoma volume affects the accuracy of computed tomographic angiography ‘spot sign' in predicting hematoma expansion after acute intracerebral hemorrhage. Eur Neurol 2011;65:150-155.
16.
Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, Molina CA, Blas YS, Dzialowski I, Kobayashi A, Boulanger JM, Lum C, Gubitz G, Padma V, Roy J, Kase CS, Kosior J, Bhatia R, Tymchuk S, Subramaniam S, Gladstone DJ, Hill MD, Aviv RI: Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol 2012;11:307-314.
17.
Mendelow AD, Gregson BA, Fernandes HM, Murray GD, Teasdale GM, Hope DT, Karimi A, Shaw MD, Barer DH: Early surgery versus initial conservative treatment in patients with spontaneous supratentorial intracerebral haematomas in the international surgical trial in intracerebral haemorrhage (STICH): a randomised trial. Lancet 2005;365:387-397.
18.
Nieuwkamp DJ, de Gans K, Rinkel GJ, Algra A: Treatment and outcome of severe intraventricular extension in patients with subarachnoid or intracerebral hemorrhage: a systematic review of the literature. J Neurol 2000;247:117-121.
19.
Ingeman A, Pedersen L, Hundborg HH, Petersen P, Zielke S, Mainz J, Bartels P, Johnsen SP: Quality of care and mortality among patients with stroke: a nationwide follow-up study. Med Care 2008;46:63-69.
20.
Delgado Almandoz JE, Yoo AJ, Stone MJ, Schaefer PW, Oleinik A, Brouwers HB, Goldstein JN, Rosand J, Lev MH, Gonzalez RG, Romero JM: The spot sign score in primary intracerebral hemorrhage identifies patients at highest risk of in-hospital mortality and poor outcome among survivors. Stroke 2010;41:54-60.
21.
Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, Khoury J: The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304-1305.
22.
Savio K, Pietra GL, Oddone E, Reggiani M, Leone MA: Reliability of the modified Rankin Scale applied by telephone. Neurol Int 2013;5:e2.
23.
Hemphill JC 3rd, Bonovich DC, Besmertis L, Manley GT, Johnston SC: The ICH score: a simple, reliable grading scale for intracerebral hemorrhage. Stroke 2001;32:891-897.
24.
Maas MB, Nemeth AJ, Rosenberg NF, Kosteva AR, Guth JC, Liotta EM, Prabhakaran S, Naidech AM: Subarachnoid extension of primary intracerebral hemorrhage is associated with poor outcomes. Stroke 2013;44:653-657.
25.
Lee SH, Kim BJ, Bae HJ, Lee JS, Lee J, Park BJ, Yoon BW: Effects of glucose level on early and long-term mortality after intracerebral haemorrhage: the Acute Brain Bleeding Analysis Study. Diabetologia 2010;53:429-434.
26.
Dowlatshahi D, Butcher KS, Asdaghi N, Nahirniak S, Bernbaum ML, Giulivi A, Wasserman JK, Poon MC, Coutts SB: Poor prognosis in warfarin-associated intracranial hemorrhage despite anticoagulation reversal. Stroke 2012;43:1812-1817.
27.
Brouwers HB, Falcone GJ, McNamara KA, Ayres AM, Oleinik A, Schwab K, Romero JM, Viswanathan A, Greenberg SM, Rosand J, Goldstein JN: CTA spot sign predicts hematoma expansion in patients with delayed presentation after intracerebral hemorrhage. Neurocrit Care 2012;17:421-428.
28.
Brouwers HB, Greenberg SM: Hematoma expansion following acute intracerebral hemorrhage. Cerebrovasc Dis 2013;35:195-201.
29.
Brouwers HB, Goldstein JN, Romero JM, Rosand J: Clinical applications of the computed tomography angiography spot sign in acute intracerebral hemorrhage: a review. Stroke 2012;43:3427-3432.
30.
Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T: Recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2005;352:777-785.
31.
Mayer SA, Brun NC, Begtrup K, Broderick J, Davis S, Diringer MN, Skolnick BE, Steiner T: Efficacy and safety of recombinant activated factor VII for acute intracerebral hemorrhage. N Engl J Med 2008;358:2127-2137.
© 2014 S. Karger AG, Basel
2014
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.