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Title: Predictors of long-term outcome after intravenous or intraarterial rtPA treatment in the Eastern
Hungarian Thrombolysis Database

Article Type: Original Article

Section/Category:

Keywords: ischemic stroke; thrombolysis; predictors; outcome

Corresponding Author: Dr.Med. Klára Edit Fekete, M.D.

Corresponding Author's Institution: University of Debrecen

First Author: Klára Fekete, MD

Order of Authors: Klára Fekete, MD; Sándor Márton, PhD; Judit Tóth, PhD; László Csiba, PhD DHAS;
István Fekete, PhD; Dániel Bereczki, PhD DHAS

Abstract: Introduction
This prospective single center study aimed to identify features determining long term outcome after
thrombolysis in a Central European stroke population.
Methods
Between the 1st of January 2004 and the 31st of December 2010, 415 patients were treated with rtPA
at the Department of Neurology, University of Debrecen. Stroke severity by the NIH stroke scale score
(NIHSSS) and imaging findings by the ASPECT score were evaluated on admission and one day later.
The modified Rankin Scale (mRS) at 3 months and case fatality at one year were evaluated.
Independent predictors of outcome were identified by multivariate testing.
Results
Data of 369 patients' were analyzed. Median NIHSSS was 12 (IQR 8; 17) on admission, and 10 (5; 16) at
24 hours. Arterial occlusion was found in 55%. Symptomatic intracerebral hemorrhage (SICH) was
detected in 3.8%. Outcome was significantly worse and SICH was more frequent in intraarterially
treated patients. At 3 months one third of the patients were independent (mRS≤2) and 23% were dead.
At one year 2 out of 3 patients were alive. Significant independent predictors of disability at 3 months
were 24 hour-NIHSSS, admission ASPECTS, admission glucose level, and treatment modality. Only the
24 hour-NIHSSS was a significant predictor of case fatality at one year.
Discussion
Although short term outcome was similar, the 3-month and one-year outcomes were worse than data
from previous reports. A more efficient healthcare program should be implemented after stroke to
maintain the favorable effect of thrombolysis in the long term.
Cover Letter
Semmelweis Egyetem Department of Neurology
Általános Orvostudományi Kar Faculty of Medicine
Neurológiai Klinika Semmelweis University
Igazgató: Dr Bereczki Dániel Head of Dept.: Dániel Bereczki
egyetemi tanár MD. PhD. DHAS
H-1083 Budapest, Balassa u.6. H-1083 Budapest, Balassa u.6.
Tel: +36-1 210 0337 Tel: +36-1 210 0337
Fax: +36-1 210 1368 Fax: +36-1 210 1368
email: bereczki@neur.sote.hu email: bereczki@neur.sote.hu



Budapest, March 10, 2014.

José Biller, MD, FACP, FAAN, FAHA

Journal of Stroke and Cerebrovascular Diseases
Loyola University Chicago
Stritch School of Medicine
Department of Neurology, Bldg. 105
2160 S. 1st Avenue
Maywood, IL 60153

Dear Professor Biller:

Attached I send the manuscript of Fekete K et al: Predictors of long-term outcome after
intravenous or intraarterial rtPA treatment in the Eastern Hungarian Thrombolysis
Database with the intention to publish it in the Journal of Stroke and Cerebrovascular
Diseases.

This report summarizes characteristics and longterm outcome of consecutively admitted 415
stroke patients treated with intravenous or intraarterial rtPA. Compared to published data
thrombolysis was similarly effective and safe in our patients in the short term, but the
outcomes at 3 months and at one year were worse. A higher proportion of large vessel
occlusion, longer time window, a higher rate of some risk factors and concomitant diseases or
suboptimal post stroke care may be responsible for the worse long term outcome in our
patients.

All authors had significant contribution to the work presented, each author has read and
approved the submission of this manuscript, and none of the authors have any relevant
conflict of interest regarding the content of the manuscript. The manuscript has never been
published before and is not under consideration by any other journals.

I hope you will find our manuscript interesting and worth to consider for publication in the
Journal of Stroke and Cerebrovascular Diseases.

Sincerely yours:

Daniel Bereczki, MD, PhD, DSc, FESO

professor of neurology
corresponding author
*Author Agreement Form
Click here to download Author Agreement Form: FeketeKlraAuthors_Agreement.pdf
*Manuscript
Click here to download Manuscript: FeketeKl+ra_JournalofSCV_text.doc Click here to view linked References

Predictors of long-term outcome after intravenous or intraarterial rtPA treatment in the

Eastern Hungarian Thrombolysis Database

Klára Fekete MD1, Sándor Márton PhD2, Judit Tóth MD PhD 3 , László Csiba MD PhD
DHAS1, István Fekete MD PhD1 , Dániel Bereczki MD PhD DHAS 4

1
Department of Neurology, Medical and Health Science Center, University of Debrecen,
Hungary,
2
Department of Sociology and Social Politics, Institute of Political Sciences and Sociology,
Faculty of Arts and Humanities, University of Debrecen, Hungary,
3
Diagnoscan Ltd., Debrecen, Hungary
4
Department of Neurology, Semmelweis University, Budapest, Hungary

Address correspondence to:

Dr. Daniel Bereczki
Department of Neurology
Semmelweis University
Budapest
Balassa u. 6.
H-1038, Hungary
Tel: +36 1 210 0337, Fax: +36 1 210 1368
E-mail: bereczki@neur.sote.hu
Key words: ischemic stroke, thrombolysis, predictors, outcome
 2

Email addresses for authors:

Klára Fekete: feketek@med.unideb.hu
Sándor Márton: marton.sandor@arts.unideb.hu
Judit Tóth: judittoth13@freemail.hu
László Csiba: csiba@med.unideb.hu
István Fekete: fekete@med.unideb.hu
Dániel Bereczki: bereczki@neur.sote.hu
 3

Abstract
Introduction
This prospective single center study aimed to identify features determining long term outcome
after thrombolysis in a Central European stroke population.
Methods
Between the 1st of January 2004 and the 31st of December 2010, 415 patients were treated
with rtPA at the Department of Neurology, University of Debrecen. Stroke severity by the
NIH stroke scale score (NIHSSS) and imaging findings by the ASPECT score were evaluated
on admission and one day later. The modified Rankin Scale (mRS) at 3 months and case
fatality at one year were evaluated. Independent predictors of outcome were identified by
multivariate testing.
Results
Data of 369 patients’ were analyzed. Median NIHSSS was 12 (IQR 8; 17) on admission, and
10 (5; 16) at 24 hours. Arterial occlusion was found in 55%. Symptomatic intracerebral
hemorrhage (SICH) was detected in 3.8%. Outcome was significantly worse and SICH was
more frequent in intraarterially treated patients. At 3 months one third of the patients were
independent (mRS≤2) and 23% were dead. At one year 2 out of 3 patients were alive.
Significant independent predictors of disability at 3 months were 24 hour-NIHSSS, admission
ASPECTS, admission glucose level, and treatment modality. Only the 24 hour-NIHSSS was
a significant predictor of case fatality at one year.
Discussion
Although short term outcome was similar, the 3-month and one-year outcomes were worse
than data from previous reports. A more efficient healthcare program should be implemented
after stroke to maintain the favorable effect of thrombolysis in the long term.
 4

Introduction
The NINDS study proved the efficacy of thrombolysis with recombinant tissue plasminogen
activator (rtPA) within 3 hours of stroke onset [1]. The ECASS 3 trial established the benefits
of intravenous (IV) rtPA in the time window of 3-4.5 hours [2], also confirmed by real life
data from the SITS ISTR registry [3]. There are only few data on predictors of long term
outcome after rtPA treatment in stroke. Favorable outcome at one year after rtPA
administration within 3 hours was reported by Kwiatowski et al. [4]. A recent meta-analysis
of data of 7012 patients indicates that IV rtPA increases the proportion of patients with
favorable outcome [5]. In the Virtual International Stroke Trials Archive (VISTA)
considerable geographical differences were seen in stroke outcome of patients participating in
clinical trials [6]. For this reason we assume that long term outcome after rtPA treatment in
stroke may also differ regionally and set forth to present patient characteristics and to identify
factors with impact on long-term outcomes of rtPA treated stroke patients in Hungary.

Methods
Subjects
Between the 1st of January 2004 and the 31st of December 2010, 415 patients were treated
with rtPA at the Department of Neurology, University of Debrecen, with a catchment area of
600,000 inhabitants and 600-700 acute stroke hospitalizations per year. For IV treatment the
time window from symptom onset was 3 hours until October 2008, and 4.5 hours afterwards.
IA use of rtPA was approved by the Local Research Ethics Committee of the University of
Debrecen with a 6-hour time-window. Cases where treatment indication did not follow the
guidelines [7, 8] were excluded and 369 patients’ data were analyzed. Four patients were lost
to long-term follow up (Figure 1.).

Database
A database was created recording age, gender, time of stroke onset, time of arrival to the
hospital, time of the CT scan result, time of administration of rtPA, previous medical history
(hypertension, diabetes mellitus, atrial fibrillation, heart failure, self reported smoking and
alcohol consumption habits), on-admission stroke severity (including the National Institute of
Health Stroke Scale Score - NIHSSS) [9], prestroke modified Rankin Scale score (mRS) [10,
11], systolic and diastolic blood pressure before the initiation of rtPA administration, serum
glucose, INR, APTT, cholesterol, triglyceride, on-admission CT/CTA scan, if performed
 5

digital subtraction angiography and a follow-up (24 hours ± 2 hours) CT scan. We registered
the NIHSS Score at 24 hours, medications for secondary prevention, mRS at 3 months, and
survival status at one-year.

Imaging
A non-contrast computed tomography (CT) was performed on admission. Arterial occlusion
(trunk or at least 1 branch of any large artery) was identified by CTA. CT was repeated one
day after treatment and in case of clinical deterioration. The Alberta Stroke Programme Early
CT Score (ASPECTS) was determined unblinded to patient characteristics and was stratified
to ≤7 (group I-severe) and above 7 (group II-mild) [12, 13]. Hemorrhagic infarction (HI) or
parenchymal hematoma (PH) were defined according to the European Cooperative Acute
Stroke Study [14, 15]. We used three definitions for symptomatic intracerebral hemorrhage
(SICH): the SITS, the ECASS and the NINDS criteria [1, 14, 16].

Treatment
IV treatment was administered according to guidelines [7, 8]. Of these 202 cases with CTA-
proven vessel occlusion IA thrombolysis was performed in 46 patients, and in 12 cases
treatment started IV and was followed by IA administration (“bridging” therapy). For IA
intervention repeated doses of 5 mg rtPA was given, until opening of the artery or the
maximum IV dose was reached. It was individually decided which treatment modality was
used by the treating physician who consulted with the neuroradiologist.

Outcomes
The NIHSSS and case fatality were evaluated the day after admission. The mRS was used to
assess outcome at 3 months and dichotomized to favorable (mRS 0-2) and unfavorable
(mRS>2 points) [17]. Survival status was evaluated at one year.

Statistical analysis
Statistical analysis was carried out using the SPSS for Windows 19.0 (SPSS Inc. Chicago,
USA). Categorical variables were assessed with Pearson χ2 test. Binary logistic regression
analysis was used to assess outcome at 3 months and at one year. Logistic regression models
were used to identify the independent predictors of 3-month disability and 1-year case fatality.
The analysis was preformed with the multivariate general linear model (GLM). In the models,
 6

disability at 3 months (mRS >2), and case fatality at one year were the dependent variables,
and those factors that were found to be associated with outcome by univariate analyses were
entered as confounding variables. In the multivariate analysis we used the following NIHSSS
categories: 0-7, 8-14, 15-22, >22. The variables were excluded from the analysis one by one,
and the variable with p> 0.05 and closest to 1.0 dropped out, until all features left in the
model had p < 0.05.

Results

Patient characteristics
Baseline characteristics are summarized in Table 1. Stroke severity and the imaging findings
on admission and one day later are shown in Figure 2. CTA identified arterial occlusion in
54.7 % of the cases. Fig. 2 presents the distribution of ASPECTS and stroke severity. There
was no difference in the distribution of risk factors between those with an ASPECT score of
≤7 or >7 on admission or at 24 hours. In those with an ASPECTS ≤7 median NIHSSS was 14
(IQR 11; 17) on admission and 12 (IQR 7; 17) one day later, whereas in those with an
ASPECT score of >7, these values were 11 (IQR 8; 17) and 3 (IQR 1; 6) respectively.

Outcome
Detailed NIHSSS changes in the first 24 hours are shown in Figure 2. At 24 hours 6% of our
patients became asymptomatic, 34% had NIHSSS ≤7 and 0.8% died. At 3 months 33% of the
patients were independent (mRS 0-2), 44% were dependent (mRS 3-5), and 23% were dead.
Case fatality at one year was 36%.

Predictors of outcome

Predictors of outcome in univariate analysis at 3 months and one year are shown in Table 2.
Redefining good outcome as mRS 0-1 instead of the predefined mRS 0-2 did not change the
conclusions. Those with favorable outcome at 3 months had a median NIHSSS of 8 and 4 on
admission and one day later, respectively, whereas those with mRS≥3 at 3 months had a
median NIHSSS of 14 both on admission and at 24 hours. Those who survived the first year
improved initially (median NIHSSS changed from 10 to 7 in the first 24 hours) whereas in
fatal cases there was no improvement during the first day (median NIHSSS was 15 initially
 7

and 16 at 24 hours). The admission ASPECTS was not associated with outcome, but those
with a score of ≤7 at 24-hours had significantly worse outcome both at 3 months and at 1 year
(p<0.001). The outcome was significantly worse in the IA group than those treated IV at 24
hours (p<0.001), at 3 months (p=0.002) and at one year (p=0.019) (Table 3.). SICH could be
detected six-times more frequently in the IA group (p<0.001).

During multivariate analysis ASPECTS on admission, admission glucose level, NIHSSS at 24

hours and treatment modality (IV or IA) retained statistical significance on 3 months
outcome. Only 24 hour-NIHSSS predicted case fatality at 1 year (p<0.001, Table 4.).

Safety parameters, adverse events

In our cohort case fatality was 0.8% at 24 hours, 23% at 3 months, and 36% at one year.
Intracerebral hemorrhage was detected in 59 patients (15.9%). The overall rate of
parenchymal hemorrhage was 7% (n=26) and hemorrhagic transformation of the infarction
was detected in 33 cases (8.9% of all subjects). The overall rate of symptomatic intracerebral
hemorrhage was 3.5% (n=13) according to both the SITS MOST and the ECASS definitions,
and 3.8% using the RCT NINDS definition. Of the 14 cases with SICH two were bedridden
and 12 were dead at 3 months, and all of them were dead at one year. Among other adverse
events orolingual angioedema occurred in 4 cases (1%), gingival bleeding in 7 cases (1.9%)
and macrohematuria not needing intervention in 2 patients (0.54%).

Discussion
The aim of this study was to find the factors that are independent predictors of long-term
outcomes after thrombolysis.

Baseline characteristics
Mean age of our patients is similar to that in France, Germany, Denmark and Switzerland, but
lower than in Greece, Italy or Sweden [6]. Hypertension and prestroke cardiac failure were
more frequent in the Hungarian sample compared to the SITS MOST study [16]. The rate of
hypertension is much higher in Hungary than in most European countries, but similar to
values reported from the USA and Canada [6]. Atrial fibrillation (16.8% in the Debrecen
region) is underrepresented compared to values in France (24.7%) and Sweden (33.3%), but
similar to data from Germany (14.1%). The occurrence of diabetes mellitus was similar to
 8

that in the ECASS 3 population (14.8 vs. 16.6%) [2]. The proportion of smokers in our cohort
is 25%, lower than reported in ECASS 3 (30.6-28.8%), or in SITS MOST (43.2%) [2, 16].

Logistic issues (onset to door time, door to needle time, onset to treatment time)
The stroke onset to treatment time of our center was 163 (127-210) minutes, whereas the
value was 140 (115-165) minutes in the SITS MOST study and 140 (90-168) minutes in the
pooled data analysis of the NINDS, the ATLANTIS, and the ECASS I-II trials [16].
Guideline recommendations aim for a less than 60 minutes door to treatment time [18]. Our
door to needle time (71±37 minutes) was similar to that in the SITS MOST study (68±30
minutes) and the study of Alvarez-Sabin (mRS 0-2: 73±14 minutes; mRS 3-6: 79±16 minutes)
[16, 19]. According to the experience in Finland, with optimal organization of prehospital and
in-hospital stroke and thrombolysis management much shorter times can be achieved [20].

Imaging
CT angiography is performed routinely in our center leading to discovering vessel occlusion
in 54.7% of the cases. In the study of Smith et al. (2009) using the same definition, large
vessel occlusion detected with CTA was responsible for 46% of the strokes [21]. In the
NINDS study CTA was not performed, the rate of large vessel occlusion was estimated as 35-
39% based on clinical criteria. The higher rate of large vessel occlusion could be one of the
reasons for the worse long term outcome in our patients.

Most of our patients had an ASPECT score of 10 before thrombolysis and even after 24 hours
an ASPECT score of 10 was found in every seventh patient on the repeated scan. The
admission ASPECTS (>7 vs≤7) was not associated with long term outcome (at 3 months
p=0.895, at one year p=0.343) in univariate analysis. Similar finding was also published by
Thomassen et al. and explained by the reversibility of some early ischemic changes [17]. The
ASPECTS at 24 hours reflecting permanent damage had a significant effect on outcome both
at 3 months and at one year (p<0.001). With multivariate analysis ASPECTS on admission
was an independent predictor at 3 months. We found a non-significant unfavorable
association of hyperglycemia (>10 mmol/L serum glucose level) with worse ASPECT score
at 24 hours (p=0.239). A recent systematic review demonstrated a relationship between on-
admission glucose level and the size of the infarct [22].
 9

Short-term outcome
Initial stroke severity in our patients (median NIHSSS: 12) was within the range of published
data of the ECASS 3 (median: 9-10) [2], the SITS MOST (median: 12) [16], and the NINDS
study (median: 14) [1]. The thrombolysis was not only effective, but safe as well. We detected
SICH in 3.8% (i.e. 23.7% of all intracerebral hemorrhages became symptomatic) after
treatment, similar to the SICH ratios in ECASS 3 (2.4% and 27%), and lower than reported in
the ECASS II of 6.2% [14], or in the NINDS study of 6-7% [1]. A Canadian thrombolysis
registry found a 4.6% SICH rate [23]. In the NINDS and ECASS II trials case fatality in
SICH cases was 50-75% in different subgroups at 3 months [14] and 61% at one year [4].
Case fatality was higher among our patients with SICH: 86% at 3 months, and 100% at one
year. It should be noted that in the NINDS and ECASS II patients were treated within 180
minutes and in a frame of a clinical trial. A recent meta-analysis also reported that those
patients benefit from the rtPA treatment who do not develop SICH and survive the acute
phase [5].
As a rarely published side affect orolingual angioedema occurred (1%) during thrombolysis,
similarly to a Canadian cohort (1.3% [23]).

Long-term outcome
In our database 1 out of 3 patients had good recovery at 3 months, and 2 out of 3 were alive at
one year. We found that the presence of hyperacute signs of ischemia by neuroimaging,
admission glucose level, and the 24 hour-NIHSSS on long-term outcome, and IA treatment
were independent predictors of disability at 3 months. A recent trial in patients with acute
ischemic stroke indicated that IA therapy is not superior to standard treatment [24]. As our
study was not randomized, the effect of IV and IA treatment cannot be compared, and the
effect of unknown or unconsidered confounders might explain the worse outcome after IA
rtPA treatment in our patients.

A recent study pointed out that 1 out of 3 stroke patients had excellent recovery at a median
time of 3 years follow up, and 1 of 3 died [25]. The NINDS study found that three out of four
thrombolysed patients were alive at one year [4], in contrast to our data where the survival
rate was lower (64.5% at one year). The most probable explanations of the worse outcome in
our cohort therefore are the longer time window (4.5 vs. 3 hours) and the higher rate of large
vessel occlusion compared to the NINDS study. Further, our study was a real world
 10

observational study, including such patients as well who should have been excluded from
clinical trials.

Our study has several limitations. The advantage is prospective data collection and detailed
information on all subjects. The number of patients involved however is limited and the study
is possibly underpowered to identify all clinically important predictors of long term outcome
after thrombolysis. This may explain why important clinical features like age, on-admission
NIHSSS, the presence of large vessel occlusion, prestroke heart failure, atrial fibrillation and
lipid-lowering therapy found to be significantly associated with long term outcome in
univariate testing, lost their statistical significance in multivariate analyses. However, even
with this relatively small number of cases, we could identify the strongest predictors of long
term outcome, i.e. severity of stroke signs 24 hours after onset, serum glucose on admission,
findings on initial neuroimaging and treatment modality.

Conclusions
Compared to international data thrombolysis was similarly effective and safe in our patients
in the short term, but the outcome at 3 months and at one year were worse. A higher
proportion of large vessel occlusion, longer time window, a higher rate of some risk factors
and concomitant diseases may be partly responsible for the worse long term outcome in our
patients. The need for a more efficient care to prevent complications after the acute phase of
stroke and the importance of early rehabilitation should also be emphasized.

Sources of funding: Grant support for D.B.: TAMOP-4.2.1.B-09/1/KMR and the National
Brain Research Program (NAP) from the government of Hungary.

Disclosure:
K.F. as assistant national coordinator for SITS EAST received travel funding for conferences
(2008-2010) (Modest)
S.M.: none
J.T.: none
L.CS.: is the national coordinator for SITS EAST, and has received fees from Boehringer
Ingelheim for giving lectures (Modest)
 11

I.F.: has received fees from Boehringer Ingelheim for giving lectures (Modest)
B.D.: has received fees for consultations for Boehringer Ingelheim (Modest)

Acknowledgments
The authors thank the medical staff taking part in the treatment.
 12

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 15

Figure legends

Figure 1. Flow chart of participants

Figure 2. Comparing on admission and 24-hour ASPECT Score and NIHSS Score

Table 1. Baseline characteristics of 369 patients

Table 2. Predictors of outcome at three months and one year by univariate analysis

Table 3. Stroke severity and outcomes by treatment modality

Table 4. Predictors of outcome in multivariate testing

Figure(s)
Click here to download Figure(s): FeketeKlFigure1.doc

Figure 1. Flow chart of participants

Figure(s)
Click here to download Figure(s): FeketeKl-Figure2.doc

Figure 2. Comparing on admission and 24-hour ASPECT Score and NIHSS Score

A./ ASPECT Score on admission and at 24 hours

B./ Stroke severity on admission and at 24 hours (NIHSS Score)

Table(s)

Table 1. Baseline characteristics of 369 patients

Feature Value

Gender (patients/%) male 217 (58.8%)

female 152 (41.2%)

Age (patients/%) ≤65 152 (41.2%)

>65 217 (58.8%)

mean±SD 67±13

male mean±SD 64±13

female mean±SD 69±13

Hypertension prior to stroke (patients/%) 267 (72.4%)

Diabetes mellitus prior to stroke 55 (14.9%)

(patients /%)

Stroke prior to stroke (patients /%) 36 (9.8%)

Atrial fibrillation prior to stroke (patients/%) 62 (16.8%)

Heart failure prior to stroke (patients/%) 67 (18.2%)

Smoker (patients/%) 95 (25.7%)

Alcohol-consumer (patients/%) 58 (15.7%)

Systolic blood pressure (mmHg, patients/%) mean±SD 150±22.3

≤140mmHg 138 (37.4%)

>140 mmHg 231 (62.6%)

mean±SD 164±13

Diastolic blood pressure (patients/%) mean±SD mmHg 83±13

≤90mm Hg 265 (71.8%)

>90 mmHg 104 (28.1%)

mean ±SD 100±6

Serum glucose (patients/%) ≤10 mmol/L 312 (84.6%)

>10 mmol/L 57 (15.4%)

Abnormal cholesterol level on admission 141(38.2%)

(patients/%)*

Abnormal triglicerid level on admission 73 (19.8%)

(patients/%) (>1.7 mmol/L)

CTA revealed vessel occlusion (patients /%) vessel occlusion 202 (54.7%)

none 167 (45.3%)

Onset to door time (minutes, mean±SD) median (IQR) 91±46

90 (60-120)

Door to needle time median (IQR) 71±37

(minutes, mean±SD) 70 (47-93)

Onset to treatment time median (IQR) 164±54

(minutes, mean±SD) 163 (127-210)

(patients/%) 0-1 hour 13 (3.5%)

1-2 hours 67 (18.2%)

2-3 hours 197 (53.4%)

3-4. 5 hours 92 (24.9%)

* For each patient it was decided individually according to the risk profile whether 5.2,
4.5mmol/L or 3.5 mmol/L was the target cholesterol level.
Table(s)

Table 2. Predictors of outcome at three months and one year by univariate analysis

Disability at 3 months Case fatality at one year

Possible predictor
OR 95% CI p OR 95% CI p

Age (>65 years) 1.997 1.285; 3.103 0.002 3.401 2.1; 5.506 <0.001

Gender 1.082 0.695; 1.683 0.728 0.852 0.549;1.323 0.476

(male vs. female)

Prestroke 0.988 0.625; 1.563 0.96 1.228 0.782; 1.929 0.371

hypertension

Prestroke heart 2.257 1.17; 4.34 0.014 1.153 0.659; 2.016 0.617

failure

Prestroke atrial 2.347 1.197; 4.608 0.013 1.904 1.092; 3.322 0.023

fibrillation

NIHSS Score on 3.511 2.514; 4.903 <0.001 2.658 1.967; 3.591 <0.001

admission

>7 vs. ≤ 7
NIHSS Score at 14.326 8.406; 24.415 <0.001 7.789 4.400; 13.786 <0.001

24 hours

>7 vs. ≤ 7

Vessel occlusion 1.244 1.079; 1.435 0.003 1.159 1.033; 1.302 0.012

Glucose 1.706 1.235; 2.385 0.001 1.381 1.025; 1.862 0.034

>10 mmol/L

Lack of 2.57 1.635; 4.038 <0.001 3.331 1.995; 5.562 <0.001

poststroke

lipid-lowering

therapy
Table(s)

Table 3. Stroke severity and outcomes by treatment modality

NIHSSS on NIHSSS at 24
3-month outcome 3- month outcome dead at 3 dead at one
Patient group admission hours SICH**
mRS 0-2* mRS 0-1* months* year*
median (IQR) ** median (IQR)**
Patients 11(8; 15.5) 9(4; 15) 2.25% 36.6% 28.3% 20.25% 33.2%
treated
intravenously
(n =311)

Patients 16(13; 18.75) 15.5 (6; 19.5) 12% 15.5% 13.8% 36.2% 48.3%
treated
intraarterially
or with
bridging
(n = 58)

All patients 12 (8; 17) 10 (5; 16) 3.8% 33.3% 26% 22.8% 35.5%
(n =369)

** p<0.001 comparing the IV and IA (including bridging) groups.

* p<0.05 comparing the IV and IA (including bridging) groups.

Table(s)

Table 4. Predictors of outcome in multivariate testing

Predictor of outcome Disability at 3 months Case fatality at one year

OR (95% CI) p OR (95% CI) p

Treatment modality 0.384 0.045 1.153 0.708
(IV vs IA) (0.150; 0.978) (0.545; 2.437)

ASPECTS on admission 1.911 0.046 0.830 0.651

(≤7 vs >7) (1.014; 5.209) (0.371; 1.855)

Glucose on admission 3.218 0.02 1.548 0.342

( >10 mmol/L vs (1.762; 4.796) (0.739; 3.245)
≤10 mmol/L vs
NIHSSS at 24 hours: 2.70x109 <0.001 107.668 <0.001
8 9
8-14 vs 0-7 (6.325x10 ; 11.651x10 ) (22.356; 518.522)
NIHSSS at 24 hours: 3.935x108 <0.001 28.376 <0.001
7 9
15-22 vs 0-7 (8.909x10 ; 1.738x10 ) (6.073; 132,581)

NIHSSS at 24 hours: 3.445x107 <0.001 9.857 <0.001

7 7
>22 vs 0-7 (3.445x10 ; 3.445x10 ) (2.143; 45.347)