Low occurrence of “spot sign” on computed tomography angiography in acute intracerebral hemorrhage: A single-center prospective study from India

Vineeth Jaison; Paramdeep Kaur; Yashpal Singh; Uttam Braino George; Jeyaraj Durai Pandian

doi:10.4103/cjhr.cjhr_102_18

ORIGINAL ARTICLE

Year : 2019 | Volume : 6 | Issue : 4 | Page : 248-253

Low occurrence of “spot sign” on computed tomography angiography in acute intracerebral hemorrhage: A single-center prospective study from India

Vineeth Jaison¹, Paramdeep Kaur², Yashpal Singh³, Uttam Braino George⁴, Jeyaraj Durai Pandian¹
¹ Department of Neurology, Christian Medical College and Hospital, Ludhiana, Punjab, India
² Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia, Vancouver, Canada
³ Department of Neurology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India
⁴ Department of Radiology, Christian Medical College and Hospital, Ludhiana, Punjab, India

Date of Submission	01-Jul-2018
Date of Decision	12-Jul-2018
Date of Acceptance	15-Aug-2018
Date of Web Publication	21-Nov-2019

Correspondence Address:
Jeyaraj Durai Pandian
Department of Neurology, Christian Medical College and Hospital, Ludhiana - 141 008, Punjab
India

Source of Support: None, Conflict of Interest: None

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DOI: 10.4103/cjhr.cjhr_102_18

Abstract

Background: Intracerebral hemorrhage (ICH) has high mortality and morbidity. The “spot sign” on three-dimensional computerized tomography angiography (3D-CTA) has been associated with hematoma expansion and poorer outcomes. The occurrence of “spot sign” in the Indian population is poorly studied. This study was done to explore the occurrence of “spot sign” in Indian patients with ICH and their outcomes. Methods: Patients with ICH presenting within 48 h from onset to the stroke unit were recruited. They underwent noncontrast computerized tomography (NCCT) head followed by 3D-CTA and a repeat NCCT head before discharge, surgery, or with clinical worsening within 7 days of presentation. Hematoma volume was calculated using the ABC/2 method. The primary outcome was modified Rankin Scale at 3 months. Results were analyzed using descriptive statistics, Fisher's exact test, independent t- test, and Mann–Whitney U-test. The analysis was performed using SPSS version 21. P < 0.05 was taken as statistically significant. Results: Fifty-four patients were recruited during the study period, and only three patients (5.6%) had “spot sign.” All patients with “spot sign” had poor outcome without hematoma expansion. Conclusion: This study shows a low occurrence of “spot sign” in patients with ICH than previously reported. All patients with “spot sign” showed poor outcome.

Keywords: Hematoma expansion, intracerebral hemorrhage, spot sign

How to cite this article:
Jaison V, Kaur P, Singh Y, George UB, Pandian JD. Low occurrence of “spot sign” on computed tomography angiography in acute intracerebral hemorrhage: A single-center prospective study from India. CHRISMED J Health Res 2019;6:248-53

How to cite this URL:
Jaison V, Kaur P, Singh Y, George UB, Pandian JD. Low occurrence of “spot sign” on computed tomography angiography in acute intracerebral hemorrhage: A single-center prospective study from India. CHRISMED J Health Res [serial online] 2019 [cited 2021 Feb 27];6:248-53. Available from: https://www.cjhr.org/text.asp?2019/6/4/248/271321

Introduction

Stroke is a leading cause of mortality and morbidity in the world today. Intracerebral hemorrhage (ICH) constitutes 10%–20% of all strokes and is the least treatable form which carries the worst outcome.^[1] There are many factors determining outcome in patients with ICH, i.e., hematoma volume, Glasgow coma scale (GCS) at presentation, presence of intraventricular extension, and age.^[2] Another important factor determining outcome is expansion of hematoma.^[3] In the past, it has been hard to predict which ICH will expand and whether any therapeutic intervention in these highly selected patient groups will show benefit.

The “spot sign” is a radiological sign that has in the recent years received some interest as a predictor for hematoma expansion.^[2] According to Thompson et al., the “spot sign” is defined as spot-like and/or serpiginous foci of enhancement, within the margin of a parenchymal hematoma without connection to outside vessels. The “spot sign” is >1.5 mm in maximal dimension and has a Hounsfield unit density at least double that of background hematoma density.”^[4]

The Asian population has a higher incidence of ICH as compared to other races.^[5] Few studies have been done on “spot sign” among the Caucasian population and even less on Asians, which show strong correlation between hematoma expansion and poor outcome.^[6],[7],[8]

The occurrence of “spot sign” in the Indian population is poorly studied.

Methods

Patients admitted to the stroke unit from February 1, 2013, to July 31, 2014, with the diagnosis of ICH, presenting within 48 h from the onset of symptoms, were recruited prospectively. All patients above 18 years of age with acute spontaneous ICH presenting to the stroke unit whose computerized tomography angiography (CTA) was done within 48 h from onset were included in this study. Patients with secondary causes of hemorrhage (e.g, aneurysmal or vascular malformation, coagulopathy, venous bleed, tumor, and traumatic), sympathomimetic-induced ICH, known chronic renal failure, and any major comorbid or terminal illness were excluded from the study. History and examination were carried out on admission on a detailed case record form, and informed consent was taken. Stroke severity was assessed using the National Institute of Health Stroke Scale (NIHSS). ICH grading was done for all patients using ICH score. All patients were screened for risk factors of ICH. All patients underwent nonenhanced brain CT scan as baseline followed by three-dimensional CTA using 128-slice Philips Ingenuity scanner. According to the protocol, 50–100 mL of nonionic contrast was given to the patients using an 18/20G Angiocath at 3.5–4 ml/sec. The presence of “spot sign” along with the site of hemorrhage was noted, and volume of the hematoma was calculated by the ABC/2 method.^[9] A repeat CT head was done before discharge, surgery, or with clinical deterioration to reassess the hematoma status within 7 days of presentation. The criteria for hematoma expansion were taken as an absolute increase in volume by 6 mL or a relative increase of 33% from the original volume.^[10] Treatment of ICH was as per the standard protocol in the stroke unit. The patients were followed in hospital, the number of hospital days, and any clinical deterioration in NIHSS score and GCS were documented. The patients were followed up from discharge to 3 months, and the outcome was assessed using the modified Rankin Scale (mRS).^[11]

Statistical analysis

All patients were divided into two groups according to the CTA findings – spot sign positive and spot sign negative. The outcome was measured as good (mRS: 0–2) or poor (mRS: 3–6) at 3 months. The statistical methods used were descriptive statistics, Fisher's exact test, independent t-test, and Mann–Whitney U-test. The means of normal distributed continuous variables were compared between the two groups using independent t-test and nonnormal variables using Mann–Whitney U-test. Fisher's exact tests were used to study the relationship between categorical variables. The analysis was performed using SPSS version 21 (IBM Corp, Armonk, NY, USA). P value was calculated between the two groups spot sign positive and spot sign negative, and P < 0.05 was considered statistically significant.

Ethical approval

The permission was taken from Institutional Ethics Committee prior to starting the project. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Results

Demography

Fifty-four patients were enrolled in this study. The mean age of all patients was 61 ± 11 years as shown in [Table 1]. There were 35 males (65%) and 19 females (35%). Median hematoma volume was 10 ml (3–38 ml, interquartile range). Of the 54 patients, 3 (5.6%) were spot sign positive [Figure 1], 7 (13.2%) showed hematoma expansion, and 36 patients (69.2%) had poor outcome; mRS ≥3. Mortality at 3 months was seen in nine patients (17.3%).

Table 1: Demographic profile and clinical features of patients with intracerebral hemorrhage

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Figure 1: Computerized tomography angiography showing (a) spot sign in brain stem, (b) serpiginous spot sign, and (c) spot sign in lobar hemorrhage, all highlighted by arrows

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Risk factors

The difference in risk factors in the two groups did not reach statistical significance [Table 2].

Table 2: Risk factors in patients with intracerebral hemorrhage

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Stroke severity

Stroke severity of all patients with ICH was moderate according to the NIHSS 14 (9–18) [Table 3]. Patients who were “spot sign” positive showed a worse NIHSS at admission and thereafter which was statistically significant (P = 0.002). GCS of the patients at presentation was 14 (11–15). Patients with “spot sign” positive showed poorer GCS at admission and thereafter in hospital which was statistically significant (P = 0.001). ICH score was 1.20 ± 1.1 for all patients at admission and showed a trend toward more severity at 1.67 ± 0.58 among patients who were “spot sign” positive, though not statistically significant.

Table 3: Radiological parameters, stroke severity and outcomes at 3 months in patients with intracerebral hemorrhage

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Radiological parameters

The median onset to CTA time in this study was 180 min (86–420 min). All patients with “spot sign” had imaging done within 6 h of onset. The hematoma volume among patients with “spot sign” was 40 ml (2.5–109 ml). Hematoma expansion was noted in 7 (13.2%) patients. None of these patients were “spot sign” positive. Among patients with ICH, 31 (57.4%) patients presented with basal ganglia hemorrhage, followed by thalamic hemorrhage in 16 (29.6%) patients and lobar hemorrhage in 6 (9.2%) [Figure 2].

Figure 2: Location of intracerebral hemorrhage in patients by number

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Outcomes

Poor mRS, as defined by mRS ≥3, was seen in 36 (69.2%) patients with ICH. Mortality was seen in 9 (17.3%) patients. All “spot sign” positives had mortality at 3 months, which was statistically significant (P < 0.0001) [Figure 3].

Figure 3: Graph depicting survival in spot sign-positive and spot sign-negative patients

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Discussion

This is the first prospective single-center study to our knowledge studying “spot sign” in patients with ICH from India. Fifty-four patients with ICH were enrolled in this study, three of whom showed positive “spot sign” (5.6%); two lobar, and one brain stem. This is a very low occurrence when compared with other studies [Table 4].^{[2],[7],[8],[10]} This difference in occurrence can be explained by the different time periods for onset to CTA. It has been shown that the incidence of spot sign decreases with time.^[12],[13] The imaging modality we used, a 128-slice Philips Ingenuity scanner is another consideration as the previous studies reported use of 64-slice scanners. The speed of scanning can also cause an underestimation of spot sign. We used only CTA source images acquired early postcontrast which is known to have lower pick up rates for “spot sign” as compared to delayed CTA, postcontrast imaging, or dynamic CTA acquisition.^{[14],[15],[16]} In our study, the median onset to CTA time was 180 (86–420 min). All “spot sign-”positive patients were within 6 h from onset. In the PREDICT study, the median onset to CTA was 134 (49–413 min) for “spot sign” positive and 172 (32–475 min) for “spot sign-”negative patients.^[2] Our study showed median onset to CTA of 240 (120–360 min) for “spot sign” positive and 180 (75–420 min) for “spot sign-”negative patients. This shows that majority of patients with ICH presented early. Possible reasons for the early presentation are the high frequency of dramatic symptoms such as weakness, dysarthria, headache, and vomiting.

Table 4: Occurrence of computerized tomography angiography spot sign in primary intracerebral hemorrhage in various studies

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Patient outcomes at 3 months from onset

In our study, majority of the patients had poor outcomes with mRS ≥3 in 36 (69.2%). All three “spot sign” positives (100%) also had poor outcome and mortality. This was statistically significant (P < 0.0001). “Spot sign” in CTA is associated with the poor outcome and mortality.^[17] According to Han et al., “spot sign” is a strong independent predictor of mortality and poor clinical outcome in primary ICH.^[7] They found that 53 of 61 (86%) “spot sign-”positive patients had poor outcomes with 35 mortalities (57.3%). The PREDICT study showed mortality in 23 of 53 (43.4%) “spot sign-”positive patients (P = 0.001).

Hematoma expansion

Seven patients (13.2%) with ICH showed hematoma expansion on follow-up CT as defined by hematoma growth of 6 ml or 33%. However, none of these were “spot sign” positive. The time window from onset to baseline CTA in these patients ranged from 1 h to 24 h, with three patients presenting beyond 3 h. Although hematoma expansion has been shown to occur more commonly within 3 h, it continues to occur up to 24 h in some cases.^[18] Mortality in ICH is strongly predicted by hematoma volume which is affected by in-hospital hematoma expansion.^[19] The spot sign score has been shown to predict hematoma expansion in various studies.^[2],[7],[10] In our study, the poor association of “spot sign” with hematoma expansion can be due to the low occurrence of “spot sign” itself and the small sample size. Our study showed higher median hematoma volume at onset 40 ml (2.5–109 ml) in “spot sign-”positive cases as compared to 8.7 ml (4–31 ml) in “spot sign-”negative cases. The PREDICT study also showed higher median ICH volume 19.9 ml (1.5–80.9 ml) in “spot sign” positive as compared to 10 ml (0.1–102.7 ml) in “spot sign-”negative cases, which was statistically significant (P < 0.001).

”Spot sign” has been studied using magnetic resonance imaging on postcontrast T1-weighted and dynamic T1-weighted images which showed “spot sign” in 46% of participants and correlated with poor outcome and showed a trend toward hematoma expansion but did not reach significance.^[20]

Strength and limitations

This is a single-center prospective study exploring the occurrence of “spot sign” in the Indian population. The occurrence of “spot sign” is surprisingly low when compared to other studies, which were done elsewhere in the world. To our knowledge, this is the first study done on a 128-slice Philips Ingenuity scanner.^[21] The small sample size makes it difficult to draw definite conclusions, but it highlights the regional variations in stroke characteristics, which must be considered before planning any large-scale interventional study in ICH using the “spot sign.”

Conclusion

This study shows a low occurrence of “spot sign” in patients presenting with primary ICH to our stroke unit. 128-slice CT scanners are faster, and early CTA may miss “spot sign.” “Spot sign” can be used as a prognostic marker for the poor outcome.

Message

The surprisingly low occurrence of “spot sign” among patients with ICH in this study warrants further investigation to plan large-scale randomized control trials using this sign as a predictor of hematoma expansion among the Indian population.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

References

1.	Feigin VL, Lawes CM, Bennett DA, Barker-Collo SL, Parag V. Worldwide stroke incidence and early case fatality reported in 56 population-based studies: A systematic review. Lancet Neurol 2009;8:355-69.
2.	Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, Molina CA, Blas YS, Dzialowski I, et al. 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;11:307-14.
3.	Rodriguez-Luna D, Rubiera M, Ribo M, Coscojuela P, Piñeiro S, Pagola J, et al. Ultraearly hematoma growth predicts poor outcome after acute intracerebral hemorrhage. Neurology 2011;77:1599-604.
4.	Thompson AL, Kosior JC, Gladstone DJ, Hopyan JJ, Symons SP, Romero F, et al. Defining the CT angiography 'spot sign' in primary intracerebral hemorrhage. Can J Neurol Sci 2009;36:456-61.
5.	van Asch CJ, Luitse MJ, Rinkel GJ, van der Tweel I, Algra A, Klijn CJ, et al. Incidence, case fatality, and functional outcome of intracerebral haemorrhage over time, according to age, sex, and ethnic origin: A systematic review and meta-analysis. Lancet Neurol 2010;9:167-76.
6.	Park SY, Kong MH, Kim JH, Kang DS, Song KY, Huh SK, et al. Role of 'spot sign' on CT angiography to predict hematoma expansion in spontaneous intracerebral hemorrhage. J Korean Neurosurg Soc 2010;48:399-405.
7.	Han JH, Lee JM, Koh EJ, Choi HY. The spot sign predicts hematoma expansion, outcome, and mortality in patients with primary intracerebral hemorrhage. J Korean Neurosurg Soc 2014;56:303-9.
8.	Moon BH, Jang DK, Han YM, Jang KS, Huh R, Park YS, et al. Association factors for CT angiography spot sign and hematoma growth in Korean patients with acute spontaneous intracerebral hemorrhage: A single-center cohort study. J Korean Neurosurg Soc 2014;56:295-302.
9.	Kothari RU, Brott T, Broderick JP, Barsan WG, Sauerbeck LR, Zuccarello M, et al. The ABCs of measuring intracerebral hemorrhage volumes. Stroke 1996;27:1304-5.
10.	Wada R, Aviv RI, Fox AJ, Sahlas DJ, Gladstone DJ, Tomlinson G, et al. CT angiography “spot sign” predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 2007;38:1257-62.
11.	Banks JL, Marotta CA. Outcomes validity and reliability of the modified rankin scale: Implications for stroke clinical trials: A literature review and synthesis. Stroke 2007;38:1091-6.
12.	Ovesen C, Havsteen I, Rosenbaum S, Christensen H. Prediction and observation of post-admission hematoma expansion in patients with intracerebral hemorrhage. Front Neurol 2014;5:186.
13.	Dowlatshahi D, Brouwers HB, Demchuk AM, Hill MD, Aviv RI, Ufholz LA, et al. Predicting intracerebral hemorrhage growth with the spot sign: The effect of onset-to-scan time. Stroke 2016;47:695-700.
14.	Ederies A, Demchuk A, Chia T, Gladstone DJ, Dowlatshahi D, Bendavit G, et al. Postcontrast CT extravasation is associated with hematoma expansion in CTA spot negative patients. Stroke 2009;40:1672-6.
15.	Hallevi H, Abraham AT, Barreto AD, Grotta JC, Savitz SI. The spot sign in intracerebral hemorrhage: The importance of looking for contrast extravasation. Cerebrovasc Dis 2010;29:217-20.
16.	Rodriguez-Luna D, Dowlatshahi D, Aviv RI, Molina CA, Silva Y, Dzialowski I, et al. Venous phase of computed tomography angiography increases spot sign detection, but intracerebral hemorrhage expansion is greater in spot signs detected in arterial phase. Stroke 2014;45:734-9.
17.	Delgado Almandoz JE, Yoo AJ, Stone MJ, Schaefer PW, Oleinik A, Brouwers HB, et al. 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.
18.	Kazui S, Naritomi H, Yamamoto H, Sawada T, Yamaguchi T. Enlargement of spontaneous intracerebral hemorrhage. Incidence and time course. Stroke 1996;27:1783-7.
19.	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;24:987-93.
20.	Schindlbeck KA, Santaella A, Galinovic I, Krause T, Rocco A, Nolte CH, et al. Spot sign in acute intracerebral hemorrhage in dynamic T1-weighted magnetic resonance imaging. Stroke 2016;47:417-23.
21.	Du FZ, Jiang R, Gu M, He C, Guan J. The accuracy of spot sign in predicting hematoma expansion after intracerebral hemorrhage: A systematic review and meta-analysis. PLoS One 2014;9:e115777.