Original Contribution

Original and Modified Graeb Score Correlation With

Intraventricular Hemorrhage and Clinical Outcome
Prediction in Hyperacute Intracranial Hemorrhage
Daniel-Alexandre Bisson, MD, FRCPC; Mathew L. Flaherty, MD; Anwar S. Shatil MSc;
David Gladstone, MD, PhD; Dar Dowlatshahi, MD, PhD; Janice Carrozzella, MSN;
Liying Zhang, PhD; Michael D. Hill, PhD; Andrew Demchuck, PhD;
Richard I. Aviv , MBChB; for the STOP-IT and SPOTLIGHT Investigators*

Background and Purpose—The Graeb score is a visual rating scale of intraventricular hemorrhage (IVH) on noncontrast
head CT. Little data exist in the hyperacute (<6 hour) period for reliability and predictive value of the modified Graeb
Score (mGS) or the original Graeb Score (oGS) for clinical outcomes or their correlation with quantitative IVH volumes.
Methods—A retrospective analysis of multicenter prospective intracranial hemorrhage study was performed. oGS and mGS
inter-observer agreement and IVH volume correlation on the baseline noncontrast head CT were calculated by intraclass
correlation coefficient and Pearson coefficient respectively. Predictors of poor outcome (modified Rankin Scale scores
≥4) at 3 months were identified using a backward stepwise selection multivariable analysis. oGS and mGS performance
for modified Rankin Scale scores ≥4 was determined by receiver operating characteristic analysis.
Results—One hundred forty-one patients (65±12 years) with median (interquartile range) time to CT of 82.5 (70.3–157.5)
minutes were included. IVH was observed in 43 (30%) patients. Inter-observer agreement was excellent for both oGS
(intraclass correlation coefficient, 0.90 [95% CI, 0.80–0.95]) and mGS (intraclass correlation coefficient, 0.97 [95% CI,
0.84–0.99]). mGS (R=0.79; P<0.01) correlated better than oGS (R=0.71; P<0.01) with IVH volumes (P=0.02). Models
of thresholded oGS and mGS were not different from a model of planimetric baseline intracranial hemorrhage and IVH
volume for poor outcome prediction. Area under the curves were 0.70, 0.73, and 0.72, respectively.
Conclusions—Excellent correlation for oGS and mGS with IVH volume was seen. Thresholded oGS and mGS are reasonable
Downloaded from http://ahajournals.org by on May 11, 2020

surrogates for planimetric IVH volume for hyperacute intracranial hemorrhage studies.   (Stroke. 2020;51:00-00. DOI:
10.1161/STROKEAHA.120.029040.)
Key Words: cerebral intraventricular hemorrhage ◼ hematoma ◼ intracranial hemorrhage ◼ scoring methods

I ntraventricular extension of hemorrhage occurs in ≈40% of

patients with spontaneous intracerebral hemorrhage (ICH).
The presence and volume of intraventricular hemorrhage (IVH)
have been shown to predict increased morbidity and mortality.
Until recently, management of IVH was largely supportive in-
cluding treatment for increased intracranial pressures. Removal
of IVH is thought to improve long-term functional outcome1,2
by reducing intracranial pressure and ventricular wall disten-
tion and reducing neurotoxicity secondary to blood breakdown
products, but overall outcomes remain poor.3,4
While a recent trial demonstrated lack of improved func-
tional outcome with extraventricular drainage and alteplase
irrigation compared with saline alone,5 accurate IVH volume
measurement remains important because clinical outcome
and mortality worsens with IVH severity.6 A simple tool for
monitoring severity of IVH or change is important for future
IVH trials to determine who may benefit from intervention
and predict outcome. Automated IVH segmentation and quan-
tification using quantitative threshold-based tools is imprac-
tical acutely and usually requires time-consuming manual
editing of computer-generated segmentation. Technical chal-
lenges relating to discrimination between periventricular he-
matoma and abutting IVH and variable choroid calcification
result in misclassification of hematoma location and inaccu-
rate volume determination. Several semiquantitative scores,
including the original Graeb Score (oGS) and modified Graeb

Received January 12, 2020; final revision received March 10, 2020; accepted April 7, 2020.
From the Division of Neuroradiology, Department of Medical Imaging (D.-A.B., A.S.S., L.Z.) and Division of Neurology, Department of Medicine
(D.G.), Sunnybrook Health Sciences centre, and University of Toronto, Canada; Department of Neurology (M.L.F., J.P.B) and Department of Radiology
(J.C.), University of Cincinnati Academic Health Center, OH; Department of Medicine (Neurology) (D.D.) and Division of Neuroradiology, Department of
Radiology (R.I.A.), University of Ottawa, Ottawa Hospital Research Institute, Canada; and Calgary Stroke Program, Department of Clinical Neurosciences,
Department of Radiology, Hotchkiss Brain Institute, University of Calgary, Canada (M.D.H., A.D.).
*A list of all STOP-IT and SPOTLIGHT investigators is given in the Appendix.
Guest Editor for this article was Harold P. Adams, MD.
Correspondence to Richard I. Aviv, MBChB, Department of Radiology, University of Ottawa, 501 Smyth Rd, Room L2121, Ottawa, ON, Canada K1H
8L6. Email raviv@toh.ca
© 2020 American Heart Association, Inc.
Stroke is available at https://www.ahajournals.org/journal/str DOI: 10.1161/STROKEAHA.120.029040

1
 2  Stroke  June 2020
Score (mGS)7,8 were developed as surrogates of IVH volume.
The mGS is an extension of oGS including more ventricular
locations and accounting for ventricular expansion.
While mGS has shown excellent inter-observer correla-
tion, and correlated more strongly than oGS with quantitative
IVH estimation9 there is a lack of consensus whether mGS has
additional predictive value over the oGS. Whereas Morgan et
al8 reported greater mGS correlation with IVH volume and
outcome, Czorlich et al9–11 found that mGS was no better than
the oGS and unnecessarily complicated IVH assessment.
The assessment, selection, and treatment of patients in the
hyperacute phase is increasingly important as new hyperacute
trials for ICH treatment emerge using minimally invasive
techniques earlier than the traditional stability periods. Scant
data exist on oGS inter-observer agreement and on oGS and
mGS score correlation with IVH in the hyperacute period (<6
hours). Existing studies evaluate performance up to 7 days9,10
or do not indicate the time to assessment.12,13
The purpose of this study was to address these knowledge
gaps by evaluating the inter-observer reliability of oGS and
mGS, determine their correlation with IVH volume and assess
prediction of clinical outcome using data from 2 prospective
hyperacute multicenter ICH studies.
Methods
Study Participants, Scan Protocol
and Patient Follow-Up
Study participants are derived from the STOP-IT (Spot Sign for
Downloaded from http://ahajournals.org by on May 11, 2020
Predicting and Treating ICH Growth) Study and the SPOTLIGHT
(Spot Sign Selection of Intracerebral Hemorrhage to Guide
Hemostatic Therapy) Study. Studies were ethics approved in each
participating institution. Anonymized data, analytic methods, and
study materials are available on request. Each study randomized
patients with acute ICH and a CTA spot sign to hemostatic therapy
with recombinant factor VIIa or placebo, while spot-negative patients
who otherwise met the same eligibility criteria were also enrolled into
an observational arm of STOP-IT. Inclusion criteria for both studies
and the main study results have been published.14 Exclusion criteria
were secondary causes of ICH (eg, vascular malformation or tumor),
anticoagulant use, planned surgery for ICH within 24 hours, planned
withdrawal of care, or presenting Glasgow Coma Scale score <8. All
patients received baseline non- contrast CT at median (IQR [inter-
quartile range]) 86 (69–170) minutes. All patients were required to
undergo a repeat head CT scan 24±3 hours after their baseline scan or
earlier if a patient was likely to die or require hematoma evacuation
<24 hours. For the purpose of this retrospective study, the need for
patient consent was waived.
Clinical Data and Imaging Analysis
Prospective data collected included patient demographics, with base-
line and follow-up ICH and IVH volumes obtained with Quantomo
software using a user-assisted neighborhood-connected region-
growing threshold-segmentation method implemented in the Insight
Segmentation and Registration Toolkit (ITK; National Library of
Medicine, Bethesda, MD) in conjunction with freehand drawing
tools.15 oGS and mGS were scored by 2 independent and blinded
neuroradiologists on the baseline noncontrast CT. Graeb scoring of
IVH was as previously published but briefly oGS uses a 0 to 12 point
score by summing a maximum of 2 points each for third and fourth
ventricle and 4 points for each lateral ventricle.7 The mGS score uses
a 0 to 32 point system where up to 2 points are given for each of tem-
poral and occipital tip, and up to 4 points for each lateral ventricle, the
third and fourth ventricle adding to 24 points with an additional single
point for each region demonstrating expansion totaling 32 (Figure 1A
and 1B).4,8 Ninety-day modified Rankin Scale scores (mRS) were
obtained by telephone interview (STOP-IT) and in person or by tele-
phone interview (SPOTLIGHT).
Statistical Analysis
Demographic data was compared using Wilcoxon rank-sum nonpara-
metric test or Fisher exact test for continuous or categorical variables.
Inter-observer agreement for oGS and mGS was quantified using
intraclass correlation coefficient. Agreement between the averaged
oGS and mGS and between oGS/mGS and IVH volumes was cal-
culated for the 2 readers using the Pearson’s product–moment cor-
relation coefficient. A score difference of ≤3 points was considered
agreement as previously published.10 ROC analysis was performed to
explore an optimal dichotomous oGS and mGS threshold associated
with clinical outcome. Quantitative IVH volume was dichotomized
by quartiles and outcome using mRS was compared between the
fourth and lower quartiles. To search for significant predictive factors
of poor functional outcome (mRS ≥4), univariate logistic regression
analysis was conducted. In addition to study average oGS and mGS
values and specific thresholds calculated in this study, a thresholded
oGS was studied based on prior literature (oGS5; thresholded as oGS
≤5 and >5) in univariate analysis.16 Natural log-transformation was
applied where appropriate to normalize distribution. All variables
P<0.10 in the univariate analysis were advanced to a backward step-
wise selection multivariable analysis. To avoid codependence of oGS,
mGS, and IVH volume (Spearman correlation, r=0.948 and r=0.981,
respectively; P<0.0001), 4 models were tested, and R2 calculated to
determine the best model fit. Two-sided P<0.05 was considered sta-
tistically significant.
Results
Demographics
Cohort comprised 141 patients with a mean (SD) age of 65
(12) years, male sex in 78/141 (55%), and median (IQR) time
to noncontrast head CT was 86 (69–170) minutes. Location of
ICH was deep in 109 (77%) and lobar in 32 (23%). IVH was
observed in 43 (30%) patients. Demographic data for patients
with and without IVH are presented in Table 1. There were no
differences in age, sex, or race distributions between patients
with ICH with and without IVH. Patients with IVH were less
likely to have lobar ICH (P=0.03) and more likely to dem-
onstrate hydrocephalus (P=0.02) and underlying hypertension
(P=0.04) compared with those without IVH. No significant
baseline parenchymal hematoma volume difference was evi-
dent (P=0.48), although IVH contributed to an overall greater
total ICH volume (P=0.01). Patients with IVH demonstrated
median (IQR) oGS and mGS scores of 4 (2–7) and 10 (4–17),
respectively. Median baseline and follow-up (IQR) IVH and
ICH volume was 7 cc (2–15), 14 cc (7–28) and 7 cc (2–15)
and 25 cc (12–24), respectively. Median (IQR) 90-day mRS
in IVH and non-IVH patients was not significantly different; 3
(2–4) and 3 (1–4), respectively.
oGS and mGS Inter-Observer Agreement
and Correlation With IVH Volume
oGS demonstrated a high inter-observer agreement (intra-
class correlation coefficient, 0.90 for absolute agree-
ment [95% CI, 0.80–0.95]); with perfect agreement in 11
(25%) cases, and scores within 3 points in 38 (86%) cases.
Similarly, perfect inter-observer agreement was obtained in
11 (25%) mGS assessments with readers scores were within
 Bisson et al   Graeb Correlation With IVH Volume and Outcome   3

Figure 1. Seventy-seven-year old female with

chronic hypertension presenting 51 min after
ictus with right thalamic 6cc intracranial hem-
orrhage with surrounding edema exerting local
mass effect on the third ventricle with hydro-
cephalus. Intraventricular hemorrhage (IVH)
extension with IVH volume, original Graeb score
(oGS) and modified Graeb score (mGS) of 5cc,
7, and 19, respectively. Incidental small vessel
ischemic changes.

3 points in 35 (80%) cases; corresponding to a high inter- excellent correlation (R=0.92; P<0.01) between averaged
observer agreement (intraclass correlation coefficient, 0.97 oGS and mGS scores (Figure 2A).
for absolute agreement [95% CI, 0.84–0.99]). There was Both oGS (R=0.71; P<0.01) and mGS (R=0.79; P<0.01)
correlated with IVH volumes (Figure 2B and 2C), with higher
Table 1.  Demographics of Patients With and Without IVH Determined at correlation for mGS compared with oGS (P=0.02). Patients
Baseline CT Scan with Graeb scores within the lower three quartiles for both
IVH Present IVH Absent P Value oGS (R=0.56; P=0.0005) and mGS (R=0.67; P<0.0001)
showed correlation with IVH volumes; higher for mGS versus
Age, y 64.3±14.1 64.7±11.7 0.847
oGS (P=0.036).
Sex, male 20 (45.5%) 58 (59.8%) 0.113
Race 0.114 Effect of IVH Severity on Outcome and
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 Asian 4 (9.1%) 11 (12.1%) Optimal oGS and mGS Thresholds

 Black 7 (15.9%) 17 (18.7%) Patients with IVH volume in the fourth quartile (>15cc) dem-
onstrating a median 90-day mRS of 4 IQR (4–5) compared
 White 10 (22.7%) 41 (45.1%)
with those with volumes ≤15cc (median 3; IQR, 2–4); P=0.1.
 Indigenous 1 (2.3%) 3 (3.1%) mGS12 was related to poor outcome. Sensitivity and spec-
 Pacific islander 5 (11.4%) 7 (7.7%) ificity for poor outcome for dichotomized oGS5 (defined as
 Other 17 (38.6%) 17 (18.7%) threshold >5 versus ≤5) was 19% and 91%. Optimal ROC de-
rived threshold for oGS was >4 (oGS4; defined as >4; ≤4) with
ICH location
sensitivity, specificity and area under the curve (AUC) of 67%,
 Lobar 5 (11.4%) 27 (27.8%) 0.030 55%, and 62% (95% CI, 43.6%–80.6%). Optimal thresholded
 Deep 38 (86.4%) 70 (72.2%) 0.065 mGS (mGS12; defined as threshold >12 versus ≤12) was 56%
 Cerebellar 0 (0.0%) 0 (0.0%) and 70%; AUC, 63% (95% CI, 44.4%–81.2%), respectively.
 Brain stem 1 (2.3%) 1 (1.0%) 0.563
Prediction of Functional Outcome
 Hydrocephalus 7 (15.9%) 4 (4.1%) 0.016
Older age, higher ICH volume, IVH volume, total ICH
Volumes median (IQR) volumes, mGS12, and smoking history were associated
 ICH 11 (6.8–23.6) 14.3 (7.4–28.3) 0.478 with a higher risk of poor functional outcome (Table 2).
 IVH 6.5 (2.2–14.6) 0 ±0 0.000 Dichotomized oGS and mGS met criteria for inclusion in mul-
tivariate model. Multivariable analysis showed that oGS >5,
 Total 25.4 (12.2–44.2) 14.3 (7.6–28.3) 0.011
oGS >4, mGS >12, higher baseline IVH volume (OR=1.71
History [1.19–2.56]) and total ICH volume (OR=3.03 [95% CI, 1.84–
 Hypertension 37 (84.1%) 63 (64.9%) 0.040 5.30]) predicted poor outcome. A model of baseline ICH and
 Hyperlipidemia 14 (31.8%) 28 (28.9%) 0.078 mGS12 demonstrated best fit (r2 14.6%; AUC, 0.73 [95% CI,
0.64–0.81]) followed by baseline IVH and ICH volume (r2
 Myocardial infarction 0 (0.0%) 4 (4.1%) 0.172
13.7%; AUC, 0.72 [95% CI, 0.63–0.81]), oGS4 and baseline
 Diabetes mellitus 9 (20.5%) 20 (20.6%) 0.982 ICH (r2 13.0%; AUC, 0.70 [95% CI, 0.61–0.80]), and oGS5
 Atrial fibrillation 1 (2.3%) 3 (3.1%) 0.319 and baseline ICH (r2 12.7%; AUC, 0.70 [95% CI, 0.62–0.80];
Values are n (%) unless otherwise stated. ICH indicates intracranial Table 3). No significant difference in AUC was found between
hemorrhage; IQR, interquartile range; and IVH intraventricular hemorrhage. models (all P>0.05; Figure 3).
 4  Stroke  June 2020
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Figure 2. The upper panel demonstrates correlation between average original Graeb score and modified Graeb score from 2 readers. Correlation between
planimetric intraventricular hemorrhage (IVH) volume and average original Graeb score is demonstrated in the lower left panel. Correlation between plani-
metric IVH volume and average modified Graeb score at baseline CT is demonstrated in the lower right panel.

Discussion agreement for mGS reported in the present study is consistent

In a prospective cohort of acute ICH patients, we demonstrate
excellent correlation between oGS and mGS scores with high
inter-observer agreement for both scores. Both oGS and mGS
correlated strongly with baseline IVH volume. mGS was su-
perior to oGS for both inter-observer agreement and IVH
correlation. Planimetrically measured ICH and IVH volumes
and thresholded oGS5, oGS 4, and mGS12 were predictive of
clinical outcome with highest association seen for mGS and
baseline ICH volume. No difference in strength of association
was found between the 4 predictive models for poor outcome,
supporting the use of thresholded oGS and mGS as surrogates
of planimetric IVH volume.
Few studies have externally validated and compared mGS
with oGS for estimation of IVH volume and prediction of
functional outcome. None has specifically focused on the
hyperacute period. There is also incorrect attribution of the
mGS designation to other IVH scoring methods that are adap-
tations of the oGS in some studies.17,18 High inter-observer
with Hansen et el10 who reported a perfect agreement between
mGS readers in 28% with an intraclass correlation coeffi-
cient of 0.95. Similarly, Morgan et al8 demonstrated strong
inter-observer agreement for mGS of 0.94. Inter-observer
agreement data for oGS was unavailable, but we demon-
strate similar reliability of oGS to mGS. Excellent correla-
tion between oGS and mGS scores is in agreement with both
Krishnan and Czorlich et al9,11; 0.88 and 0.92, respectively.
The correlation between oGS, mGS, and planimetric IVH
volume measurements are similar to prior publications8,9 and
confirms the utility of Graeb score as a tool for semiquantita-
tive IVH grading.
IVH volume, oGS5, oGS4, and mGS12 scores but not
IVH presence were predictive of poor clinical outcome. oGS4
demonstrated higher sensitivity than mGS for outcome pre-
diction despite similar AUC while mGS showed greater speci-
ficity. oGS may, therefore, be preferable as a screening tool to
identify patients with worse outcome. However, if an invasive
 Bisson et al   Graeb Correlation With IVH Volume and Outcome   5

Table 2.  Univariate Predictors of Poor Functional Outcome (mRS Score ≥4) 0.74 for mGS compared with oGS for prediction of poor out-
Predictive Factors P Value OR (95% CI) come.10 Hwang demonstrated similar performance of oGS for
clinical outcome prediction to Morgan.19 Czorlich showed that
Male sex 0.0814 0.53 (0.26–1.08)
mGS underperformed for Glasgow outcome scale determina-
Age, y 0.0330 1.03 (1.00–1.07) tion relative to oGS (0.767 versus 0.780).13 In another study,
IVH presence 0.2835 1.52 (0.71–3.26) the addition of mGS to a predictive clinical model previously
oGS (continuous) 0.0765 1.51 (0.96–2.40) failed to significantly improve outcome prediction,12 and oGS
tertiles were not significantly associated with either 30 day
oGS >5 vs ≤5 0.0993 2.39 (0.86–7.03)
mortality or 6 month good outcome.16 Three prior publica-
oGS >4 vs ≤4 0.0547 2.60 (0.99–7.13) tions have demonstrated that an OGS cutoff of 5 predicted the
mGS (continuous) 0.1316 1.28 (0.93–1.77) rate of functional outcome, consistent with our findings.12,13,16
mGS ≤12 vs >12 0.0332 3.44 (1.14–11.67) No prior study has calculated an optimal mGS threshold as-
sociated with worse clinical outcome. The finding that oGS4,
ICH volume at baseline (log) 0.0007 2.11 (1.39–3.34)
oGS5, and mGS12 added to a model of baseline ICH demon-
IVH volume at baseline (log) 0.0306 1.45 (1.04–2.05) strated similar prediction for poor outcome compared with a
Total ICH volume (log) <0.0001 2.58 (1.64–4.26) model of planimetric IVH confirms the utility of each of these
Deep ICH 0.8515 1.08 (0.48–2.52) scores as a surrogate of quantitative IVH.
The very small median IVH volume of 7cc in our pa-
Hypertension 0.0816 2.10 (0.93–5.02)
tient cohort (IVH volumes between 2 and 15cc in 50%) could
Diabetes mellitus 0.8024 1.12 (0.46–2.66) explain the disparity between outcome prediction of IVH
Angina 0.8203 0.75 (0.03–8.08) volume, thresholded oGS and mGS and IVH presence as a
Myocardial infarction 0.8081 0.74 (0.03–7.92) binary variable. Worse functional outcomes are expected with
greater IVH severity but the role of smaller IVH volumes
Atrial fibrillation 0.1811 4.77 (0.59–98.01)
is less well understood. Whereas some reports suggest any
Hypercholesterolemia 0.8925 1.06 (0.48–2.29) IVH is associated with increased risk6,20 others demonstrate
Transient ischemic attack 0.5601 1.53 (0.35–6.75) that small IVH volumes are not associated with worse out-
Smoking 0.0368 2.30 (1.07–5.13) come.12,13 Trifan and Nishikawa et al showed that low volumes
ICH indicates intracranial hemorrhage; IVH, intraventricular hemorrhage;
of IVH (defined as oGS <5) had similar outcomes to patients
mGS, modified Graeb score; mRS, modified Rankin Scale; oGS, original Graeb with ICH without IVH19 and were not associated with poor
Downloaded from http://ahajournals.org by on May 11, 2020

score; and OR, odds ratio.
surgical intervention is planned mGS may be superior due to a
lower number of false positives. Contradictory data exist as to
the utility of oGS and mGS. Morgan reported a higher AUC of
functional outcome.12,15 Consistent with this understanding,
the association between IVH volume and outcome in this se-
ries was driven by the patients within the highest quartile for
IVH volume. Comparative studies assessing IVH prediction
on stability scans, imaged at variable but generally extended

Table 3.  Four Predictive Models for Poor Outcome Prediction Derived From a Backward Stepwise Selection Process

Predictive Factors Coefficient SE of Coefficient P Value OR (95% CI) R2, %

Model A with oGS >5 12.67%
 Intercept −2.7834 0.6879 <0.0001
 oGS (>5 vs ≤5) 1.2095 0.5599 0.0308 3.35 (1.14–10.51)
 Baseline ICH volume (log) 0.8384 0.2347 0.0004 2.31 (1.49–3.76)
Model B with oGS >3.5 12.95%
 Intercept −2.7542 0.6827 <0.0001
 oGS (>3.5 vs ≤3.5) 1.1807 0.5255 0.0246 3.26 (1.18–9.50)
 Baseline ICH volume (log) 0.8193 0.2334 0.0004 2.27 (1.47–3.68)
Model C with mGS >11.5 14.62%
 Intercept −2.8908 0.6905 <0.0001
 mGS (>11.5 vs ≤11.5) 1.6701 0.6274 0.0078 5.31 (1.63–19.85)
 Baseline ICH volume (log) 0.8669 0.2356 0.0002 2.38 (1.53–3.88)
Model D 13.67%
 Intercept −2.8494 0.6928 <0.0001
 IVH volume at baseline (log) 0.4485 0.1835 0.0145 1.57 (1.10–2.28)
 Baseline ICH volume (log) 0.8238 0.2345 0.0004 2.78 (1.47–3.70)
ICH indicates intracranial hemorrhage; IVH, intraventricular hemorrhage; mGS, modified Graeb score; oGS, original Graeb score; and OR, odds ratio.
 6  Stroke  June 2020
Figure 3. Receiver operating curves (ROC) for 4 models including model
A and B (original Graeb score [oGS >5 and >3.5] and intracranial hemor-
rhage), model C (modified Graeb score [mGS] >11.5 and ICH), and model
D (planimetric baseline intraventricular hemorrhage volume, and plani-
metric baseline intracranial hemorrhage volume) for poor (modified Rankin
Scale score ≥4) 90-day functional outcome.
time points <24 hour, <72 hours, and up to 7 days.8–13,18 In
Downloaded from http://ahajournals.org by on May 11, 2020
contrast, the present study had a short median time to scan of
82.5 minutes which may account for why IVH presence and
average (nondichotomized) oGS and mGS scores were insen-
sitive to final outcome because smaller IVH volumes and less
IVH expansion are expected hyperacutely.
Limitations of the study include the relatively small
sample size. Small sample sizes in published IVH studies
are due to the relative infrequency of both primary ICH as
a stroke subtype and the additional infrequency of super-
imposed IVH. Prior data sources include a single cohort
study of aneurysmal subarachnoid hemorrhage patients
with IVH (n=150),11 prospective registry10 (n=71), retro-
spective single center studies (n=35 oGS only),12 (n=112;
oGS only),13 (n=153; oGS only18), and post hoc analysis of
CLEAR B (Clot Lysis Evaluating Accelerated Resolution
of Intraventricular Hemorrhage Clinical Trial) (n=36
patients, 360 scans) and VISTA (Virtual International
Stroke Trials Archive) (n=399).8,9 Despite, small sample
size, the prospective multicenter study design and hyper-
acute time period of the study are strengths rarely seen in
prior publications. A proportion of patients in this study
received recombinant factor VIIa which could theoreti-
cally have contributed to the lack of IVH growth and lack
of association of IVH presence with outcome. However,
recombinant factor VIIa was not shown to alter size of ei-
ther ICH or IVH compared with controls in SPOTLIGHT
and STOP-IT studies14; and therefore, this factor is un-
likely to have influenced the predictive findings.
In summary, we demonstrate excellent correlation for
oGS and mGS with IVH volume. Models of oGS4, oGS5, and
mGS12 were not significantly different from a model of plan-
imetric IVH and ICH volume for prediction of clinical out-
come supporting the use of either thresholded oGS or mGS as
a surrogate for IVH volume. This finding mitigates technical
difficulties associated with IVH measurement and allows for
rapid semiquantitative estimation which is more translatable
to the emergency setting. mGS is associated with higher inter-
observer agreement and correlation with IVH volume and
may be preferable to oGS.
Appendix
Kevin E. Thorpe, Mmath, Dalla Lana School of Public Health,
University of Toronto; Jane C. Khoury, PhD, Applied Health
Research Centre; Heidi J. Sucharew, PhD, University of Cincinnati;
Fahad Al-Ajlan, MD, King Faisal Specialist Hospital and Research
Center, Riyadh, Saudi Arabia; Ken Butcher, MD, PhD, University of
New South Wales, Sydney, Australia; Gord Gubitz, MD, Dalhousie
University, Halifax, Nova Scotia, Canada; Stephanie DeMasi, BSc,
MSc, Applied Health Research Centre, Li Ka Shing Knowledge
Institute of St Michael’s Hospital; Judith Hall, MSc, Applied Health
Research Centre, Li Ka Shing Knowledge Institute of St Michael’s
Hospital; David Gregg, MD, Medical University of South Carolina,
Charleston; Muhammad Mamdani, PharmD, Applied Health Research
Centre, Li Ka Shing Knowledge Institute of St Michael’s Hospital;
Michel Shamy, MD, University of Ottawa; Richard H. Swartz, MD,
PhD, Division of Neurology, Department of Medicine, University
of Toronto; C. Martin del Campo, MD, Division of Neurology,
Department of Medicine, University of Toronto; Brett Cucchiara,
MD, University of Pennsylvania, Philadelphia; Peter Panagos, MD,
Washington University in St Louis, St Louis, Missouri; Joshua N.
Goldstein, MD, Massachusetts General Hospital, Boston; Edward
C. Jauch, MD, Mission Research Institute, Mission Health System,
Asheville, North Carolina; Joseph P. Broderick, MD, University of
Cincinnati Academic Health Center, Cincinnati.
Sources of Funding
The SPOTLIGHT (Spot Sign Selection of Intracerebral Hemorrhage
to Guide Hemostatic Therapy) trial was funded by peer-reviewed
operating grants from the Canadian Institutes of Health Research,
the Ontario Stroke Network, and the Ontario Ministry of Research
and Innovation. The STOP-IT (Spot Sign for Predicting and
Treating ICH Growth) trial was funded by a peer-reviewed oper-
ating grant from the National Institute of Neurological Disorders
and Stroke. Recombinant activated coagulation factor VII was pur-
chased with grant funds for the SPOTLIGHT sites from Canadian
Blood Services and Hema-Quebec and was supplied by Novo
Nordisk for the STOP-IT sites. Dr Gladstone is supported by a Mid-
Career Award from the Heart and Stroke Foundation of Canada, the
Eaton Scholar Award from the University of Toronto Department
of Medicine, Bastable-Potts Chair in Stroke Research, the Tory
Family, and the Department of Medicine at Sunnybrook Health
Sciences Centre. Drs Broderick and Flaherty were supported by
grant P50 NS044283 from the National Institute of Neurological
Disorders and Stroke. R.I. Aviv was funded by a project grant from
Canadian Institutes of Health Research.
Disclosures
Dr Gladstone has received grants from the Canadian Institutes of
Health Research, Ontario Ministry of Research and Innovation, and
Ontario Stroke Network. Dr Demchuk has received personal fees
from Medtronic and NovoNordisk Canada. Dr Dowlatshahi has re-
ceived grants from the Heart and Stroke Foundation of Canada and
has a patent issued for automated dynamic spot sign detection soft-
ware. J. Carrozzella received a grant from University of Cincinnati.
 Bisson et al   Graeb Correlation With IVH Volume and Outcome   7
Dr Flaherty has received nonfinancial support for the STOP-IT trial
from Novo Nordisk and personal fees from CSL Behring, Janssen
Pharmaceuticals, and Portola Pharmaceuticals and has a patent issued
and licensed to Sense Diagnostics for a noninvasive cerebral nervous
system sensor that can monitor intracranial bleeding. The other
authors report no conflicts.
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