Prediction of long term functional outco
Atherosclerosis 203 (2009) 228–235
Prediction of long-term functional outcome in patients with acute
ischemic non-embolic stroke
John Protopsaltis a , Stelios Kokkoris a , Panagiotis Korantzopoulos b,∗ , Haralampos J. Milionis c ,
Efthalia Karzi d , Alexandra Anastasopoulou e , Kostantina Filioti a , Stavros Antonopoulos a ,
Andreas Melidonis f , Grigorios Giannoulis a
a
Second Department of Internal Medicine, ‘Tzanio’ General Hospital of Piraeus, Piraeus, Greece
Department of Cardiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
c Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
d Department of Computed Tomography, ‘Tzanio’ General Hospital of Piraeus, Piraeus, Greece
e Department of Neurology, ‘Tzanio’ General Hospital of Piraeus, Piraeus, Greece
f Diabetes Center, ‘Tzanio’ General Hospital of Piraeus, Piraeus, Greece
b
Received 5 March 2008; received in revised form 18 May 2008; accepted 26 May 2008
Available online 7 July 2008
Abstract
In a prospective observational study, we assessed the relative value of conventional stroke risk factors and emerging markers in the prediction
of functional outcome of patients surviving the acute phase of an ischemic non-embolic stroke. All available eligible patients consecutively
admitted due to a first-ever acute ischemic non-embolic stroke during a 2-year period were evaluated. In a total of 105 patients (54 males,
51 diabetic) a series of clinical, biochemical and imaging characteristics were recorded, including demographic data, blood pressure, serum
glucose, insulin, lipids, inflammatory markers, intima–media thickness of the carotid arteries (IMT), brain damage location and size of the
infarct volume. Barthel Activities of Daily Living Index (BI) scale was used to assess the severity of neurological deficit on admission and
the functional outcome 6 months after discharge. Brain infarct volume, stroke location in the anterior circulation, age, diabetes mellitus,
IMT and plasma interleukin-1 levels proved to be significant determinants of long-term functional outcome, assessed by BI disability score.
ROC curve analyses indicated that the infarct volume is superior to other predictors in the diagnosis of patients with unfavorable functional
outcome (BI < 95) at 6 months post-discharge (area under the curve, AUC = 0.80, 95% confidence interval 0.64–0.95; p = 0.003). Significant
differences in the mean infarct volume were noted among age tertiles, with the diabetic patients in the 3rd tertile of age experiencing the
worst outcome (LSD test, p = 0.019). Taken together, the assessment of infarct volume seems to have a significant predictive value regarding
long-term functional outcome, especially in the elderly diabetic patients.
© 2008 Elsevier Ireland Ltd. All rights reserved.
Keywords: Ischemic stroke; Functional outcome; Infarct volume; Predictor
1. Introduction
Ischemic stroke is characterized by a great variation
in terms of clinical outcome. Epidemiological evidence
suggests several risk factors for ischemic stroke, including hypertension, tobacco smoking, diabetes mellitus, atrial
fibrillation, while novel markers have been implicated as pre∗
Corresponding author. Tel.: +30 26510 99347; fax: +30 26510 97017.
E-mail address: p.korantzopoulos@yahoo.gr (P. Korantzopoulos).
0021-9150/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.atherosclerosis.2008.05.042
dictors of acute brain ischemia [1]. The relationships of either
‘conventional’ or ‘emerging’ risk factors with the functional
outcome remains to be established [2].
There is evidence that inflammation plays an important
role in the pathophysiology of ischemic stroke and markers of
inflammation, such as C-reactive protein (CRP) and cytokine
levels (interleukin, IL-1 and IL-6) may well serve as prognostic factors for neurological worsening in stroke patients
[3,4]. In this setting, several imaging modalities, including
computed tomography (CT) scan, and common carotid artery
J. Protopsaltis et al. / Atherosclerosis 203 (2009) 228–235
intima–media thickness (CCA-IMT) have also been tested
as predictors of functional outcome [5,6]. Finally, the stroke
subtype, namely embolic strokes in patients with a known cardiac source, has been associated with a poor overall prognosis
[7].
The evaluation of clinical, biochemical and imaging markers that may correlate with the functional recovery and
long-term prognosis could prove useful in the early and
post-discharge management of subjects suffering an acute
ischemic stroke. In the present study, we prospectively investigated the relative value of conventional stroke risk factors
and emerging markers in the prediction of functional outcome of patients surviving the acute phase of an ischemic
non-embolic stroke.
2. Subjects and methods
2.1. Study design
All available eligible subjects with a first-ever acute
ischemic non-embolic stroke consecutively admitted to the
Departments of Internal medicine and Neurology of ‘Tzanio’
General Hospital from February 2004 to January 2006 were
prospectively studied.
Patients were classified as having a definite new stroke if
evidence of sudden onset’s neurological symptoms (aphasia,
dysarthria, diplopia or hemiparesis) lasted >24 h. Subjects
with a history of vascular disease (previous stroke, carotid
surgery, angina, myocardial infarction, revascularizations,
and peripheral artery disease), active infections, neoplasias,
acute or chronic inflammatory conditions were excluded from
the study.
A brain CT scan was performed within 24 h of admission to exclude patients with intra-cerebral hemorrhage. A
second brain CT scan was performed on the 7th day after
admission in order to compute cerebral infarct volume. Infarct
volume was measured in cubic centimeters according to
the formula: 0.5 × A × B × C, where A and B represent the
greatest perpendicular diameters and C represents the number of sections of 10 mm where the cerebral infarct was
apparent.
To increase the accuracy of prediction model, we restricted
our patient selection to more homogeneous groups in terms of
stroke subtype, excluding patients with cardioembolic stroke,
given that these strokes have a worse prognosis. Participants
were assessed for a definite cardiac source of embolism,
including those with atrial fibrillation or flutter, bacterial or
marantic endocarditis, recent myocardial infarction, valvular heart disease, atrial myxoma, intracardiac thrombus,
and cardiomyopathy. All subjects underwent transthoracic
echocardiography, and in selective cases transoesophangeal
echocardiography and/or brain magnetic resonance imaging
(MRI). Brain MRI was performed within 6 h of onset, only
when clinical and CT findings were highly suggestive of
intra-cerebral hemorrhage.
229
The sudden onset of focal neurological deficit was also
taken into consideration. Patients who died within the first 6
months after stroke onset were also excluded from the study
as patients with a transient ischemic attack (i.e. neurological
deficit lasting 102 cm in men and >88 cm in women), high TG levels
(≥150 mg/dL), low HDL-cholesterol levels (
Prediction of long-term functional outcome in patients with acute
ischemic non-embolic stroke
John Protopsaltis a , Stelios Kokkoris a , Panagiotis Korantzopoulos b,∗ , Haralampos J. Milionis c ,
Efthalia Karzi d , Alexandra Anastasopoulou e , Kostantina Filioti a , Stavros Antonopoulos a ,
Andreas Melidonis f , Grigorios Giannoulis a
a
Second Department of Internal Medicine, ‘Tzanio’ General Hospital of Piraeus, Piraeus, Greece
Department of Cardiology, School of Medicine, University of Ioannina, 45110 Ioannina, Greece
c Department of Internal Medicine, School of Medicine, University of Ioannina, Ioannina, Greece
d Department of Computed Tomography, ‘Tzanio’ General Hospital of Piraeus, Piraeus, Greece
e Department of Neurology, ‘Tzanio’ General Hospital of Piraeus, Piraeus, Greece
f Diabetes Center, ‘Tzanio’ General Hospital of Piraeus, Piraeus, Greece
b
Received 5 March 2008; received in revised form 18 May 2008; accepted 26 May 2008
Available online 7 July 2008
Abstract
In a prospective observational study, we assessed the relative value of conventional stroke risk factors and emerging markers in the prediction
of functional outcome of patients surviving the acute phase of an ischemic non-embolic stroke. All available eligible patients consecutively
admitted due to a first-ever acute ischemic non-embolic stroke during a 2-year period were evaluated. In a total of 105 patients (54 males,
51 diabetic) a series of clinical, biochemical and imaging characteristics were recorded, including demographic data, blood pressure, serum
glucose, insulin, lipids, inflammatory markers, intima–media thickness of the carotid arteries (IMT), brain damage location and size of the
infarct volume. Barthel Activities of Daily Living Index (BI) scale was used to assess the severity of neurological deficit on admission and
the functional outcome 6 months after discharge. Brain infarct volume, stroke location in the anterior circulation, age, diabetes mellitus,
IMT and plasma interleukin-1 levels proved to be significant determinants of long-term functional outcome, assessed by BI disability score.
ROC curve analyses indicated that the infarct volume is superior to other predictors in the diagnosis of patients with unfavorable functional
outcome (BI < 95) at 6 months post-discharge (area under the curve, AUC = 0.80, 95% confidence interval 0.64–0.95; p = 0.003). Significant
differences in the mean infarct volume were noted among age tertiles, with the diabetic patients in the 3rd tertile of age experiencing the
worst outcome (LSD test, p = 0.019). Taken together, the assessment of infarct volume seems to have a significant predictive value regarding
long-term functional outcome, especially in the elderly diabetic patients.
© 2008 Elsevier Ireland Ltd. All rights reserved.
Keywords: Ischemic stroke; Functional outcome; Infarct volume; Predictor
1. Introduction
Ischemic stroke is characterized by a great variation
in terms of clinical outcome. Epidemiological evidence
suggests several risk factors for ischemic stroke, including hypertension, tobacco smoking, diabetes mellitus, atrial
fibrillation, while novel markers have been implicated as pre∗
Corresponding author. Tel.: +30 26510 99347; fax: +30 26510 97017.
E-mail address: p.korantzopoulos@yahoo.gr (P. Korantzopoulos).
0021-9150/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.atherosclerosis.2008.05.042
dictors of acute brain ischemia [1]. The relationships of either
‘conventional’ or ‘emerging’ risk factors with the functional
outcome remains to be established [2].
There is evidence that inflammation plays an important
role in the pathophysiology of ischemic stroke and markers of
inflammation, such as C-reactive protein (CRP) and cytokine
levels (interleukin, IL-1 and IL-6) may well serve as prognostic factors for neurological worsening in stroke patients
[3,4]. In this setting, several imaging modalities, including
computed tomography (CT) scan, and common carotid artery
J. Protopsaltis et al. / Atherosclerosis 203 (2009) 228–235
intima–media thickness (CCA-IMT) have also been tested
as predictors of functional outcome [5,6]. Finally, the stroke
subtype, namely embolic strokes in patients with a known cardiac source, has been associated with a poor overall prognosis
[7].
The evaluation of clinical, biochemical and imaging markers that may correlate with the functional recovery and
long-term prognosis could prove useful in the early and
post-discharge management of subjects suffering an acute
ischemic stroke. In the present study, we prospectively investigated the relative value of conventional stroke risk factors
and emerging markers in the prediction of functional outcome of patients surviving the acute phase of an ischemic
non-embolic stroke.
2. Subjects and methods
2.1. Study design
All available eligible subjects with a first-ever acute
ischemic non-embolic stroke consecutively admitted to the
Departments of Internal medicine and Neurology of ‘Tzanio’
General Hospital from February 2004 to January 2006 were
prospectively studied.
Patients were classified as having a definite new stroke if
evidence of sudden onset’s neurological symptoms (aphasia,
dysarthria, diplopia or hemiparesis) lasted >24 h. Subjects
with a history of vascular disease (previous stroke, carotid
surgery, angina, myocardial infarction, revascularizations,
and peripheral artery disease), active infections, neoplasias,
acute or chronic inflammatory conditions were excluded from
the study.
A brain CT scan was performed within 24 h of admission to exclude patients with intra-cerebral hemorrhage. A
second brain CT scan was performed on the 7th day after
admission in order to compute cerebral infarct volume. Infarct
volume was measured in cubic centimeters according to
the formula: 0.5 × A × B × C, where A and B represent the
greatest perpendicular diameters and C represents the number of sections of 10 mm where the cerebral infarct was
apparent.
To increase the accuracy of prediction model, we restricted
our patient selection to more homogeneous groups in terms of
stroke subtype, excluding patients with cardioembolic stroke,
given that these strokes have a worse prognosis. Participants
were assessed for a definite cardiac source of embolism,
including those with atrial fibrillation or flutter, bacterial or
marantic endocarditis, recent myocardial infarction, valvular heart disease, atrial myxoma, intracardiac thrombus,
and cardiomyopathy. All subjects underwent transthoracic
echocardiography, and in selective cases transoesophangeal
echocardiography and/or brain magnetic resonance imaging
(MRI). Brain MRI was performed within 6 h of onset, only
when clinical and CT findings were highly suggestive of
intra-cerebral hemorrhage.
229
The sudden onset of focal neurological deficit was also
taken into consideration. Patients who died within the first 6
months after stroke onset were also excluded from the study
as patients with a transient ischemic attack (i.e. neurological
deficit lasting 102 cm in men and >88 cm in women), high TG levels
(≥150 mg/dL), low HDL-cholesterol levels (