A Dark Side of Subcortical Diffusion-Weighted Lesions?
Characteristics, Cause, and Outcome in Large Subcortical Infarction:
The Bergen Norwegian Stroke Cooperation Study
Christopher Elnan Kvistad, MD; Halvor Oygarden, MD; Nicola Logallo, MD, PhD;
Gunnar Moen, MD; Lars Thomassen, MD, PhD; Ulrike Waje-Andreassen, MD, PhD;
Halvor Naess, MD, PhD
Downloaded from http://stroke.ahajournals.org/ by guest on October 2, 2016
Background and Purpose—Diffusion-weighted imaging (DWI) is highly accurate in identifying and locating ischemic
stroke injury. Few studies using DWI have investigated large subcortical infarctions (LSIs). We aimed to study clinical
characteristics, cause, and outcome in patients with ischemic stroke with LSI diagnosed on DWI and compare these with
those who had lacunar DWI lesions or DWI lesions located elsewhere.
Methods—Patients with stroke admitted between February 2006 and July 2013 were prospectively registered in a stroke
database and examined with DWI. Patients with DWI lesions classified as LSI (subcortical, ≥15 mm) were compared
with those with lacunar lesions (subcortical, <15 mm, lacunar infarction [LI]), cortical lesions (cortical infarction [CI]),
or no LSI, which included LI, CI, mixed cortical–subcortical, cerebellar, brain stem, and combined lesion locations.
Results—A total of 1886 patients with ischemic stroke were included, of which 128 patients (6.8%) had LSI, 317 (16.8%) LI,
and 544 (28.8%) CI. The no LSI group included 1758 patients. Occlusive pathology in the proximal middle cerebral artery
was more frequent in patients with acute stroke with LSI. Lacunar syndrome was associated with LSI when compared
with CI and no LSI. Unknown cause was frequent in the LSI group (60.4%) and independently associated with LSI in the
LSI versus LI (P<0.001), LSI versus CI (P=0.002), and LSI versus no LSI population (P<0.001). LSI was independently
associated with unfavorable outcome, whether compared with LI (P=0.002), CI (P<0.001), or no LSI (P=0.002).
Conclusions—LSI is associated with distinct clinical characteristics, unknown cause, and unfavorable outcome, which
separates this stroke entity from patients with lacunar subcortical DWI lesions or DWI lesions located elsewhere. (Stroke.
2014;45:2710-2716.)
Key Words: cerebral infarction ◼ diffusion-weighted MRI ◼ subcortical vascular lesion
I
schemic stroke affecting subcortical regions is frequent
and often occurs as small infarcts caused by small-vessel
disease. This stroke subgroup named lacunar infarction (LI)
is well studied and has been associated with pre-existing diseases such as hypertension and diabetes mellitus.1 Most studies
have shown a high rate of favorable outcome after LI, although
increasing evidence suggests a worse prognosis with time.2
There are, however, several patients presenting with subcortical infarction who do not fall under the category of LI.
These lesions are larger than lacunar lesions and may not be
caused by small-vessel disease. Our knowledge of these large
subcortical infarctions (LSIs) is limited. Clinical characteristics and cause have mostly been studied in smaller series
performed in the 1980s or 1990s and often without being compared with other stroke subtypes or locations.3–8 One exception
was a Dutch trial, where no differences were found regarding
clinical features or risk factor profiles in patients with LSIs
as compared with lacunar (LIs) or cortical infarctions (CIs)
diagnosed with computed tomography (CT).9 Because several patients with stroke are without sign of infarction on CT,
stroke localization and classification may be inaccurate.10
Diffusion-weighted imaging (DWI) has proved to be highly
sensitive and specific in detecting and locating ischemic injury
and has revolutionized the concept of neuroimaging within
stroke research.11 In this study, we aimed to identify clinical
characteristics, cause, and outcome in patients with LSI on
DWI and compare these with patients who had lacunar subcortical DWI lesions or lesions located elsewhere.
Methods and Patients
All patients with ischemic stroke admitted to the Stroke Unit,
Department of Neurology, Haukeland University Hospital in Bergen,
Received April 11, 2014; final revision received June 23, 2014; accepted June 23, 2014.
From the Departments of Neurology (C.E.K., H.O., N.L., L.T., U.W.-A., H.N.) and Radiology (G.M.), Haukeland University Hospital, Bergen, Norway;
Department of Clinical Medicine, University of Bergen, Bergen, Norway (C.E.K., L.T.); and Centre of Age-Related Medicine, Stavanger University
Hospital, Stavanger, Norway (H.N.).
The online-only Data Supplement is available with this article at http://stroke.ahajournals.org/lookup/suppl/doi:10.1161/STROKEAHA.
114.005781/-/DC1.
Correspondence to Christopher Elnan Kvistad, MD, Department of Neurology, Haukeland University Hospital, University of Bergen, N-5021 Bergen,
Norway. E-mail echr@helse-bergen.no
© 2014 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.114.005781
2710
Kvistad et al A Dark Side of Large Subcortical DWI Lesions 2711
Downloaded from http://stroke.ahajournals.org/ by guest on October 2, 2016
Norway, between February 2006 and July 2013 were prospectively
registered in a database (The Bergen Norwegian Stroke Cooperation
Registry). MRI and MR angiography were in general performed
<1 day after admission unless any contraindications were present.
Contraindications included pacemaker, none-consenting, or unstable
patient. CT angiography was performed in patients potentially eligible
for recanalizing treatment. Patients with DWI lesions because of ischemic stroke were included in the study after informed consent had
been obtained. The study was approved by the local ethics committee.
Clinical characteristics, medical history, and stroke cause were
registered by a stroke neurologist <1 day after admission. Cause was
determined by the Trial of Org 10172 in Acute Stroke Treatment
(TOAST) classification.12 Stroke severity was measured using the
National Institutes of Health Stroke Scale (NIHSS). NIHSS score
was measured on admission, repeatedly during the first 24 hours and
at discharge. NIHSS was measured by certified stroke neurologists
or stroke nurses. Progressive neurological symptoms were defined
as a worsening of ≥2 NIHSS points at any time within the first 24
hours after hospital admission. ΔNIHSS was defined as the difference between NIHSS on admission and at discharge. Based on presenting symptoms, patients were classified according to the Oxford
Community Stroke Project classification.13 An additional retrospective analysis was performed to compare rates of the most common
lacunar syndromes (pure motor hemiparesis, pure sensory stroke, sensimotor stroke, and ataxic hemiparesis) in patients with LSI and LI.14
Symptomatic extracranial internal carotid artery stenosis was defined
as ≥70% stenosis based on percentage of area reduction at duplex
ultrasonography. Outcome was defined by the modified Rankin Scale
(mRS) score at day 7 or at discharge, if discharged earlier. Favorable
outcome was defined as mRS 0 to 1 and good outcome as mRS 0 to
2. Patients were also scored with the Barthel Index on day 7 or at
discharge, if discharged earlier.
Neuroimaging
DWI was performed as part of a routine MRI protocol for patients with
stroke on 1.5-T Siemens Magnetom (Symphony, Erlangen, Germany).
The DWI sequence used was ep2d_diff:3scan_trace, with the following specification of parameters: field of view 230 mm, slice thickness 5 mm, TR 3200 ms, TE 94 ms, voxel size 1.8×1.8×5.0 mm, scan
time 1:12, sample average (number of excitations): 3 and b-values
0, 500 and 1000 s/mm2. Additional sequences were t2_flair_tra and
ep2e_diff_3scan_trace_ADC.
LSI was present if DWI lesions were located in the hemispheric
white matter, basal ganglia, internal capsule, thalamus, or corona radiate with a diameter ≥15 mm. LI was defined as DWI lesions in the
same territory as LSI with a diameter <15 mm. CI was defined as
DWI lesions confined to the supratentorial cortex. Mixed cortical–
subcortical infarction included DWI lesions that were both cortical
and subcortical in the supratentorial region. Cerebellar and brain stem
infarction were present if DWI lesions were located in cerebellum
or brain stem, respectively. Patients were allocated into 4 different
groups according to DWI localization: LSI, LI, CI, and all DWI lesions except LSI (no LSI). The no LSI group included LI, CI, mixed
cortical–subcortical, cerebellar, and brain stem infarction. This group
also comprised patients with >1 DWI location, such as patients with
concomitant cortical and cerebellar infarctions. Patients with LSI
were categorized into 4 different territories: lenticulostriate territory
(including nucleus lentiformis, caput of the caudate nucleus, and anterior limb and genu of the internal capsule), anterior choroidal artery
territory (including cauda of the caudate nucleus and posterior limb
of the internal capsule), thalamic territory (including the thalamus),
white matter medullary branches territory (including hemispheric
white matter). Total occlusion of intracranial arteries was defined as
100% occlusion. Intracranial stenosis was based on lumen reduction
at CT angiography or MR angiography and defined as partial occlusion.15 Stenosis <20% was considered normal. Recanalization on MR
angiography was defined as complete recanalization of the primary
occlusion with normal distal flow. Neuroimaging was reviewed by a
stroke neurologist (H.N.) with >15 years experience in interpretation
of stroke CT and MRI.
Statistical Analyses
Univariate analyses were performed with clinical characteristics,
cause, and outcomes where patients in the LSI group were compared
with the LI group, CI group, and no LSI group. Student t test or
Mann–Whitney U test was used for continuous variables when appropriate. χ2 test was used for categorical variables. Logistic regression analyses were performed to identify clinical characteristics and
cause associated with LSI within the 3 different patient populations:
LSI versus LI, LSI versus CI, and LSI versus no LSI. Analyses were
performed by stepwise backward elimination where first step included all parameters that turned out significant (P<0.05) in the univariate analyses. Logistic regression analyses were also performed with
favorable outcome (mRS 0–1) versus unfavorable outcome (mRS
2–6) as dependent variable to assess the relationship between LSI
and clinical outcome within the patient populations LSI versus LI,
LSI versus CI, and LSI versus no LSI. Analyses were performed by
stepwise backward elimination where potential confounders for favorable or unfavorable outcome were included in first step analyses.
Age and sex were forced into each regression analysis to adjust for
these potentially confounding factors.
Results
In total, 2412 patients had ischemic stroke during the study
period. MRI was performed in 1979 (82.1%) of these patients.
Patients without MRI examination were older (79.4 versus
69.0 years; P<0.001), had higher NIHSS scores on admission
(11.4 versus 4.9; P<0.001), and a lower proportion of favorable outcome (84 [19.4%] versus 874 [44.3%]; P<0.001).
A total of 1886 patients examined with MRI had DWI
lesions and were included in the study.
There were 128 patients (6.8%) with LSI, 317 (16.8%) with
LI, 544 (28.8%) with CI, 484 (25.7%) with mixed cortical–
subcortical infarction, 98 (5.2%) with cerebellar infarction,
136 (7.2%) with brain stem infarction, and 179 (9.5%) with a
combination of >1 infarct location. Accordingly, 128 patients
were included in the LSI group, 317 in the LI group, 588 in
the CI group, and 1758 in the no LSI group. In patients with
LSI, 61 patients (47.7%) had DWI lesions in lenticulostriate
territory, 29 (22.7%) in anterior choroidal artery territory, 8
(6.3%) in thalamic territory, and 30 (23.4%) in white matter
medullary branches territory.
Clinical Characteristics
Univariate analyses of clinical characteristics are presented in
Table 1. Distribution of age and sex were similar between the
LSI group and the other 3 groups. Prior medical history was
similar between the groups, except fewer smokers (P=0.014)
and more patients with atrial fibrillation (P=0.003) in the LSI
group than in the LI group. Median admission stroke severity as measured by the NIHSS score was higher in patients
with LSI as compared with patients with LI (P<0.001), CI
(P<0.001), and no LSI (P=0.025). Higher NIHSS score on
admission (odds ratio [OR], 1.13; P<0.001), clinical presentation as partial anterior circulation infarct (OR, 3.02;
P<0.001), and symptomatic internal carotid artery stenosis
(OR, 7.98; P=0.004) were independently associated with LSI
as compared with LI (Table 2). Patients with LSI had a higher
NIHSS score (OR, 1.11; P<0.001) and systolic blood pressure (OR, 1.01; P<0.001) on admission and more frequently
presented as lacunar infarct (LACI; OR, 2.56, P<0.001)) when
compared with patients with CI. Similarly, LSI was associated
with higher NIHSS score (OR, 1.04; P=0.005) and systolic
2712 Stroke September 2014
Table 1. Univariate Analyses of Clinical Characteristics, Cause, and Outcome in Patients With Ischemic Stroke With LSI as
Compared With Patients With LI, CI, and No LSI
LSI
(n=128)
LI
(n=317)
CI
(n=544)
No LSI
(n=1758)
P1
(LSI vs LI)
P2
(LSI vs CI)
P3
(LSI vs No LSI)
69.3 (13.0)
67.5 (13.7)
74 (57.8)
183 (57.7)
70.8 (14.1)
69.0 (14.7)
0.110
0.136
0.415
334 (61.4)
1060 (60.3)
0.987
0.455
589 (162–1291)
163 (90–464)
0.580
195 (93–754)
0.007
0.228
0.781
Clinical characteristics
Age, y, mean (SD)
Male sex, %
Time from symptom onset to
admission, min, median (IQR)
210 (101–1131)
Definite time of
symptom onset, %
66 (51.6)
178 (56.2)
348 (64.0)
998 (56.8)
0.379
0.009
0.251
Woke up with stroke, %
24 (18.8)
77 (24.3)
73 (13.4)
268 (15.2)
0.207
0.123
0.290
120 (93.8)
281 (88.6)
489 (89.9)
1559 (88.7)
0.102
0.178
0.076
7 (5.5)
31 (9.8)
44 (8.1)
167 (9.5)
0.141
0.314
0.128
Hypertension
72 (56.3)
168 (53.0)
263 (48.4)
897 (51.1)
0.533
0.112
0.261
Diabetes mellitus
16 (12.5)
44 (14.0)
78 (14.4)
244 (14.0)
0.674
0.580
0.641
Daily smoking
27 (21.1)
102 (32.9)
123 (23.3)
469 (28.1)
0.014
0.824
0.090
Atrial fibrillation
27 (21.1)
33 (10.4)
156 (26.7)
447 (25.4)
0.003
0.083
0.275
Ischemic heart disease
14 (10.9)
18 (5.7)
79 (14.5)
230 (13.1)
0.052
0.291
0.485
Ischemic stroke
11 (8.6)
32 (10.4)
73 (13.6)
206 (11.9)
0.574
0.124
0.262
Prior functional status, %
Living in own residence,
independent
Downloaded from http://stroke.ahajournals.org/ by guest on October 2, 2016
Living in own residence or
nursery home, dependent
Prior medical history, %
Clinical features on presentation
NIHSS score, median (IQR)
4 (1–8)
3 (1–4)
2 (0–5)
3 (1–6)
<0.001
<0.001
0.025
Progressive neurological
symptoms, %
39 (30.5)
65 (20.5)
70 (12.9)
370 (21.1)
0.025
<0.001
0.013
Progressive neurological
symptoms in those admitted
<6 h after onset, %
15 (38.5)
19 (27.9)
30 (12.6)
146 (24.5)
0.261
<0.001
0.052
Systolic blood pressure,
mm Hg, mean (SD)
170.6 (28.5)
175.4 (30.9)
159.8 (28.9)
163.6 (29.6)
0.066
<0.001
0.005
Diastolic blood pressure,
mm Hg, mean (SD)
89.4 (16.9)
92.8 (18.8)
86.2 (17.3)
86.9 (17.8)
0.039
0.030
0.059
OCSP, %
TACI
16 (12.5)
1 (0.3)
30 (5.5)
207 (11.8)
<0.001
0.005
0.806
PACI
59 (46.1)
73 (23.0)
358 (65.8)
731 (41.6)
<0.001
<0.001
0.318
LACI
45 (35.2)
200 (63.1)
95 (17.5)
402 (22.9)
<0.001
<0.001
0.002
POCI
8 (6.3)
42 (13.3)
60 (11.0)
412 (23.4)
0.034
0.107
<0.001
63 (19.9)
187 (34.5)
564 (32.2)
<0.001
0.759
0.377
Intracranial occlusions and recanalization, %
Performed CT angiography
on admission
Complete M1 occlusion
46 (35.9)
0 (0)
7 (3.7)
68 (12.1)
0.001
0.001
0.292
Partial M1 occlusion
10 (21.7)
1 (1.6)
8 (4.3)
29 (5.1)
0.001
<0.001
<0.001
Complete/partial
M1 occlusion
18 (39.1)
1 (1.6)
15 (7.9)
97 (17.1)
<0.001
<0.001
<0.001
121 (94.5)
290 (91.8)
492 (90.4)
1571 (89.4)
0.315
0.141
0.065
Performed MR
angiography on d 1
8 (17.4)
Complete recanalization after
complete M1 occlusion
2 (25.0)
0
6 (85.7)
24 (37.5)
N/A
0.019
0.488
Complete recanalization
after partial/complete
M1 occlusion
5 (27.8)
0 (0)
8 (53.3)
33 (35.9)
0.539
0.135
0.509
(Continued )
Kvistad et al A Dark Side of Large Subcortical DWI Lesions 2713
Table 1. Continued
LSI
(n=128)
LI
(n=317)
CI
(n=544)
No LSI
(n=1758)
P1
(LSI vs LI)
P2
(LSI vs CI)
P3
(LSI vs No LSI)
Ultrasound ICA, %
>70% symptomatic stenosis
10 (8.3)
3 (1.0)
45 (9.0)
146 (9.3)
<0.001
0.827
0.726
17 (13.3)
22 (6.9)
107 (19.7)
304 (17.3)
0.032
0.094
0.243
Trombolytic treatment, %
IV-tPA
Cause by TOAST, %
Large artery
17 (13.3)
5 (1.6)
89 (16.4)
228 (13.0)
<0.001
0.371
0.919
Cardioembolic
30 (23.4)
13 (4.1)
206 (37.9)
545 (31.0)
<0.001
0.002
0.073
Small-vessel disease
1 (0.8)
193 (60.9)
1 (0.2)
253 (14.4)
<0.001
0.264
<0.001
Other
2 (1.6)
1 (0.3)
16 (2.9)
54 (3.1)
0.146
0.385
0.331
78 (60.9)
104 (32.8)
231 (42.5)
672 (38.2)
<0.001
<0.001
<0.001
mRS 0–1, %
37 (28.9)
166 (52.4)
331 (60.9)
776 (44.2)
<0.001
<0.001
0.001
mRS 0–2, %
65 (50.8)
244 (77.0)
433 (79.6)
1148 (65.3)
<0.001
<0.001
0.001
NIHSS at discharge,
median (IQR)
3 (1–7)
1 (0–3)
1 (0–2)
2 (0–5)
<0.001
<0.001
0.002
ΔNIHSS improvement at
admission and discharge,
median (IQR)
0 (0–2)
1 (0–2)
1 (0–3)
1 (0–2)
0.175
0.015
0.116
75.3 (30.4)
90.6 (19.5)
91.5 (20.6)
82.3 (29.5)
<0.001
<0.001
0.005
Unknown
Outcome
Downloaded from http://stroke.ahajournals.org/ by guest on October 2, 2016
Barthel score at discharge,
mean (SD)
CI indicates cortical infarction; CT, computed tomography; ICA, internal carotid artery; IQR, interquartile range; IV-tPA, intravenous tissue-type plasminogen activator;
LACI, lacunar infarct; LI, lacunar infarction; LSI, large subcortical infarction; mRS, modified Rankin Scale; NIHSS, National Institutes of Health Stroke Scale; no LSI, all
infarctions except LSI; OCSP, Oxford Community Stroke Project; PACI, partial anterior circulation infarct; POCI; posterior circulation infarct; TACI, total anterior circulation
infarct; and TOAST, Trial of Org 10172 in Acute Stroke Treatment.
blood pressure (OR, 1.01; P=0.042) on admission and clinical
presentation as LACI (OR, 1.89; P=0.002) when compared
with patients with no LSI.
CT angiography on admission was performed in 46 (35.9%)
patients with LSI, of which 27 (58.7%) had normal findings,
8 (17.4%) had complete M1 occlusion, 10 (21.7%) had partial M1 occlusion, and 1 (2.2%) had complete M2 occlusion
(Table 1). Occlusive pathology in M1 (complete or partial
occlusion) was more frequent in patients with LSI (18; 39.1%)
as compared with those with LI (1 [1.6%]; P<0.001), CI (15
[7.9%]; P<0.001), or no LSI (97 [17.1%]; P<0.001). The rate
of recanalization on MR angiography in patients with complete M1 occlusion was lower in patients with LSI as compared with patients with CI (P=0.019).
Cause
More patients in the LSI group (17; 13.3%) had large artery disease as compared with the LI group (5 [1.6%]; P<0.001; Table 1).
Cardioembolism was also more frequent in patients with LSI
(30; 23.4%) than in patients with LI (13 [4.1%]; P<0.001), yet
less frequent than in patients with CI (206 [37.9%]; P=0.002).
A total of 78 patients (60.9%) had unknown stroke cause in
the LSI group, which was higher than the proportion in the
LI (104 [32.8%]; P<0.001), CI (231 [42.5%]; P<0.001), and
no LSI group (672 [38.2%]; P<0.001). There were no differences in proportions of large artery disease (P=0.554), cardioembolism (P=0.103), or unknown cause (P=0.238) among the
different territories in patients with LSI. Cause with TOAST
classification was similar in patients with LSI and occlusive
pathology versus LSI and no occlusive pathology, except a borderline significant increase of large-vessel disease in patients
with occlusion (5 [27.8%] versus 12 [10.9%]; P=0.051).
Unknown cause was independently associated with LSI in
the LSI versus LI (OR, 3.75; P<0.001), LSI versus CI (OR,
1.95; P=0.002), and LSI versus no LSI population (OR, 2.69;
P<0.001; Table 2).
Outcome
Progressive neurological symptoms was more frequent in
patients with LSI (39; 30.5%) as compared with patients with
LI (65; 20.5%; P=0.025), CI (70; 12.9%; P=0.001), and no LSI
(370; 21.1%; P=0.013; Table 1). LSI was independently associated with unfavorable outcome when adjusted for confounders
in the LSI versus LI (OR, 2.31; P=0.002), LSI versus CI (OR,
4.33; P<0.001), and LSI versus no LSI (OR, 2.08; P=0.002)
population (Table 3). Unfavorable outcome was particularly
high in patients with LSI and DWI lesions in anterior choroidal
artery territory. A total of 27 patients (93.1%) in this group had
unfavorable outcome as compared with 44 (72.1%) in lenticulostriate territory, 4 (50.0%) in thalamic territory, and 16 (53.3%)
in white matter medullary branches territory (P=0.004).
Discussion
Prior studies of LSI have mainly used CT for infarct localization without having compared LSI with other stroke subtypes or locations.3–9 In our study, all patients included were
2714 Stroke September 2014
Table 2. Relationship Between LSI and Clinical
Characteristics in Logistic Regression Analyses Among
Different Patient Populations (LSI vs LI, LSI vs CI, and
LSI vs No LSI)
OR
95% Confidence
Interval
P
Value
LSI vs LI (n=445)
Age
1.01
0.99–1.03
0.243
Sex
1.04
0.62–1.74
0.888
<0.001
NIHSS on admission
1.13
1.06–1.20
Symptomatic ICA stenosis ≥70%
7.98
1.92–33.11
PACI
3.02
1.82–5.01
<0.001
Unknown stroke cause
3.75
2.28–6.18
<0.001
0.004
LSI vs CI (n=672)
Downloaded from http://stroke.ahajournals.org/ by guest on October 2, 2016
Age
0.98
0.96–0.99
0.007
Sex
1.07
0.69–1.64
0.776
NIHSS score on admission
1.11
1.07–1.16
<0.001
Systolic BP on admission
1.01
1.01–1.02
<0.001
LACI
2.56
1.62–4.06
<0.001
Certain time of symptom onset
1.78
1.17–2.72
0.008
Unknown cause
1.95
1.26–3.00
0.002
LSI vs no LSI (n=1886)
Age
1.00
0.99–1.02
0.656
Sex
1.06
0.72–1.55
0.775
NIHSS score on admission
1.04
1.01–1.08
0.005
Prior independency
2.72
1.21–6.08
0.015
Systolic BP on admission
1.01
1.00–1.01
0.042
LACI
1.89
1.26–2.84
0.002
Unknown cause
2.69
1.84–3.94
<0.001
For stepwise backward selection procedure, see Table I in the online-only Data
Supplement. BP indicates blood pressure; CI, cortical infarction; ICA, internal
carotid artery; LACI, lacunar infarct; LI, lacunar infarction; LSI, large subcortical
infarction; NIHSS, National Institutes of Health Stroke Scale; no LSI, all infarctions
except LSI; OR, odds ratio; and PACI, partial anterior circulation infarct.
examined with DWI. We showed that patients with LSI differed from patients with lacunar subcortical DWI lesions or
patients with DWI lesions located elsewhere as to clinical
characteristics, cause, and outcome, emphasizing the distinctive features of this specific ischemic stroke subtype.
There were several clinical characteristics associated with
LSI, such as neurological worsening. Prior studies have
reported that 20% to 30% of patients with lacunar stroke experience neurological worsening within the first hours or days
after stroke onset.16,17 The exact pathophysiology behind this
mechanism is uncertain, but explanations based on hemodynamic factors, inflammation, and extension of thrombosis have
been proposed.18 Our study may add new insights into this phenomenon because neurological worsening was more frequent
in patients with LSI as compared with the other groups, including LI. Because major occlusion seems to be a frequent cause
of LSI, this could suggest that neurological worsening may be
because of other mechanisms than those directly associated
with lacunar stroke.
Clinical presentation of patients with LSI as classified by the
Oxford Community Stroke Project scale also differed from the
other groups. Oxford Community Stroke Project is a widely
used stroke classification system, which categorizes neurological deficits into 4 different stroke syndromes and may assist in
predicting arterial occlusion location and clinical outcome.19,20
Our study showed that LSI was associated with LACI when
compared with patients with CI or no LSI, and partial anterior
circulation infarct when compared with patients with LI. This
is in line with another study that showed that ≈16% of those
with lacunar syndrome did not have LI. A high proportion of
these patients had atherotrombotic or cardioembolic infarction,
indicating that lacunar syndromes could be caused by more
extensive nonlacunar infarctions, such as LSI.21 In concordance with a prior study, we found a lower rate of pure sensory
stroke in LSI as compared with LI.22 Nevertheless, our findings indicate that several patients presenting with LACI have
larger subcortical lesions and not lacunar lesions, which often
is caused by small-vessel disease. This highlights the importance of performing DWI in patients presenting with LACI.
Our study showed that a majority of patients with LSI either
had normal CT angiography findings on admission or occlusive pathology in the proximal middle cerebral artery. The high
rate of normal angiographic findings may suggest that several
patients with LSI experience recanalization before admission.
Alternatively, it suggests that LSI may occur because of other
mechanisms than major occlusions, similar to the pathophysiology behind smaller LIs such as in situ atheroma or lipohyalinosis.2,23 However, the high frequency of middle cerebral artery
occlusions in patients with LSI suggests other contributing
mechanisms than that of lacunar stroke. These findings are also
in conformity with prior transcranial Doppler studies that have
shown a relatively high frequency of middle cerebral artery
occlusions in patients with large striatocapsular infarctions.3,8
Our study showed that complete recanalization on day one was
achieved in relatively few patients with LSI with middle cerebral
artery occlusion. This is in contrast to another study that showed
that persistent middle cerebral artery occlusion frequently leads
to CI.24 A developed collateral circulation may have prevented
CI in our patients with LSI and middle cerebral artery occlusion.
Stroke cause is important because different causes are
treated differently for secondary stroke prevention.25 In our
study, large artery disease, cardioembolism, and unknown
stroke cause were more frequent in LSI than in LI, showing
that larger subcortical lesions may have other causes than
smaller lacunar lesions. More than half of the patients with
LSI had unknown stroke cause, and LSI was also associated
with unknown stroke cause when compared with CI and no
LSI. These findings are in concordance with another study
that investigated the association of DWI lesion patterns with
TOAST stroke subtypes.26 The authors reported that nearly
half (11 of 23) of the patients with large subcortical lesions
were classified with an unknown TOAST cause. As in our
study, a possible explanation may be that several of these
patients actually may have had small-vessel disease. However,
as the definition of this specific TOAST subtype has a cutoff
size limit of <15 mm, they cannot be defined as small-vessel
disease by using the TOAST classification. Recent studies
have, however, questioned the validity of using a 15-mm limit
in DWI lesions, because the original TOAST classification
lesions were based on CT findings and not DWI.26–28
Kvistad et al A Dark Side of Large Subcortical DWI Lesions 2715
Table 3. Relationship Between LSI and Favorable Outcome (mRS 0–1)/Unfavorable Outcome (mRS 2–6) in Logistic Regression
Analyses Among Different Patient Populations (LSI vs LI, LSI vs CI, and LSI vs No LSI)
OR (95% Confidence Interval)
Unadjusted
LSI vs LI (n=445)
LSI vs CI (n=672)
LSI vs no LSI (n=1886)
P Value
Adjusted
Favorable outcome
0.37 (0.24–0.57)
0.43 (0.26–0.73)*
Unfavorable outcome
2.70 (1.74–4.20)
2.31 (1.37–3.91)*
Favorable outcome
0.26 (0.17–0.40)
0.23 (0.14–0.38)†
Unfavorable outcome
3.82 (2.51–5.81)
4.33 (2.63–7.13)†
Favorable outcome
0.51 (0.35–0.76)
0.48 (0.31–0.76)‡
Unfavorable outcome
1.94 (1.32–2.89)
2.08 (1.32–3.27)‡
Unadjusted
Adjusted
<0.001
0.002*
<0.001
<0.001†
0.001
0.002‡
For stepwise backward selection procedure, see Table II in the online-only Data Supplement. CI indicates cortical infarction; LI, lacunar infarction; LSI, large subcortical
infarction; mRS, modified Rankin Scale; and no LSI, all infarctions except LSI.
*Adjusted for age, sex, National Institutes of Health Stroke Scale (NIHSS) on admission, serum glucose on admission, and prior independency.
†Adjusted for age, sex, NIHSS score on admission, and prior independency.
‡Adjusted for age, sex, NIHSS score on admission, serum glucose on admission, prior independency and intravenous treatment with tissue-type plasminogen activator.
Downloaded from http://stroke.ahajournals.org/ by guest on October 2, 2016
Our study showed an independent association between LSI
and unfavorable outcome as compared with patients with LI,
CI, and no LSI. In support of these findings, patients with
LSI also performed worse on Barthel Index at discharge. This
may partly be explained by the larger size of DWI lesions in
the LSI group, resulting in increased baseline stroke severity and consequently worse outcomes. However, associations
between LSI and unfavorable outcome were sustained when
adjusting for initial stroke severity, indicating other contributing mechanisms as well. Such a mechanism may rely on
the large number of axons concentrated in subcortical white
matter tracts, including the pyramid. Large infarctions affecting these areas may thus cause worse outcomes as compared
with cortical lesions of similar size. Cortical functions are
spread out over larger regions, and unaffected cortical areas
may compensate for damaged cortical areas.29,30 Studies have
also shown an ability of perilesional reorganization in cortical lesions resulting in improved chances of recovery.31 These
mechanisms may not be present in LSIs, leading to more
damage caused by infarction. Prior studies have also shown
an association between subcortical infarcts and focal cortical
thinning with neuropsychological impairment.32–34 In theory,
this could contribute to a worse long-term prognosis with
cognitive decline in patients with subcortical infarcts, which
may be worse in patients with larger subcortical infarcts considering the potentially larger number of disrupted axons as
compared with smaller lacunar infarcts. Differences in cortical atrophy and cognitive deficits between LSI and LI could be
a relevant topic for future studies.
Our findings are in contrast to 2 other studies of LSI.9,35
A Dutch trial reviewed patients with LSI of presumed noncardioembolic origin on CT.9 Clinical features and risk factor
profiles were similar in patients with LSI as compared with
those with LIs or CIs. Clinical outcomes were not assessed,
but stroke recurrence rates were similar. In contrast to our
study, patient recruitment was limited to patients with transient
ischemic attack or minor ischemic attack, and neuroimaging
was performed by CT and not MRI. These factors may partly
explain the different results from our study. Another study
investigated outcomes of patients with LSI on MRI or CT as
compared with patients with lacunar, atherothrombotic, and
cardioembolic infarctions.35 Short-term outcome was worse in
patients with LSI than that of LIs, but better than atherothrombotic or cardioembolic infarction. Unlike our study, patients
with LSI were mainly compared with other stroke causes and
not with other stroke locations.
There are some limitations in our study. We only included
patients where MRI had been performed and ≈18% of the
total ischemic stroke population registered was thus excluded.
Contraindications to MRI included nonconsenting, which is
more frequent in severe ischemic stroke. This is also supported by the more severe neurological deficits on admission
in patients not examined with MRI. The generalizability of
our results may, therefore, be limited. Second, size of DWI
lesions was not measured, except subcortical DWI lesions,
which were differentiated between LSI (≥15 mm) and LI (<15
mm). However, prior studies have shown a strong association
between DWI lesion size and neurological deficits as measured
by NIHSS on admission.29,36 We adjusted for NIHSS score on
admission in all logistic regression analyses with favorable
outcome as dependent variable. It, therefore, seems unlikely
that patients with LSI solely had worse outcomes because of
larger DWI lesions. Third, only short-term outcome was registered and not outcome after 90 days. Short-term outcomes are,
however, highly relevant in acute ischemic stroke, because
long-term outcome also encompasses other factors such as
rehabilitation and secondary infections. Short-term outcome
is, therefore, more related to the stroke as such.37
Strengths of the study include stroke location classification exclusively with MR DWI and the use of prospectively
included patients in a stroke registry.
In conclusion, LSI is associated with distinct clinical characteristics, unknown cause, and unfavorable outcome, which
separates this stroke entity from patients with lacunar DWI
lesions or DWI lesions located elsewhere.
Sources of Funding
Dr Kvistad has been supported by Helse Vest Research Fund no.
911776 as a PhD research fellow.
Disclosures
None.
2716 Stroke September 2014
References
Downloaded from http://stroke.ahajournals.org/ by guest on October 2, 2016
1. You R, McNeil JJ, O’Malley HM, Davis SM, Donnan GA. Risk factors
for lacunar infarction syndromes. Neurology. 1995;45:1483–1487.
2.Norrving B. Long-term prognosis after lacunar infarction. Lancet
Neurol. 2003;2:238–245.
3. Weiller C, Ringelstein EB, Reiche W, Thron A, Buell U. The large striatocapsular infarct. A clinical and pathophysiological entity. Arch Neurol.
1990;47:1085–1091.
4. Donnan GA, Bladin PF, Berkovic SF, Longley WA, Saling MM. The stroke
syndrome of striatocapsular infarction. Brain. 1991;114(pt 1A):51–70.
5. Bladin PF, Berkovic SF. Striatocapsular infarction: large infarcts in the
lenticulostriate arterial territory. Neurology. 1984;34:1423–1430.
6. Nicolai A, Lazzarino LG, Biasutti E. Large striatocapsular infarcts: clinical features and risk factors. J Neurol. 1996;243:44–50.
7.Levine RL, Lagreze HL, Dobkin JA, Turski PA. Large subcortical
hemispheric infarctions. Presentation and prognosis. Arch Neurol.
1988;45:1074–1077.
8. Horowitz DR, Tuhrim S. Stroke mechanisms and clinical presentation in
large subcortical infarctions. Neurology. 1997;49:1538–1541.
9. Halkes PH, Kappelle LJ, van Gijn J, van Wijk I, Koudstaal PJ, Algra
A. Large subcortical infarcts: clinical features, risk factors, and longterm prognosis compared with cortical and small deep infarcts. Stroke.
2006;37:1828–1832.
10. Jauch EC, Saver JL, Adams HP Jr, Bruno A, Connors JJ, Demaerschalk
BM, et al; American Heart Association Stroke Council; Council on
Cardiovascular Nursing; Council on Peripheral Vascular Disease; Council
on Clinical Cardiology. Guidelines for the early management of patients
with acute ischemic stroke: a guideline for healthcare professionals from
the American Heart Association/American Stroke Association. Stroke.
2013;44:870–947.
11. Donnan GA, Davis SM. Neuroimaging, the ischaemic penumbra, and selection of patients for acute stroke therapy. Lancet Neurol. 2002;1:417–425.
12. Adams HP Jr, Bendixen BH, Kappelle LJ, Biller J, Love BB, Gordon
DL, et al. Classification of subtype of acute ischemic stroke. Definitions
for use in a multicenter clinical trial. TOAST. Trial of Org 10172 in
Acute Stroke Treatment. Stroke. 1993;24:35–41.
13. Bamford J, Sandercock P, Dennis M, Burn J, Warlow C. Classification
and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337:1521–1526.
14.Arboix A, Martí-Vilalta JL. Lacunar stroke. Expert Rev Neurother.
2009;9:179–196.
15. Samuels OB, Joseph GJ, Lynn MJ, Smith HA, Chimowitz MI. A standardized method for measuring intracranial arterial stenosis. AJNR Am J
Neuroradiol. 2000;21:643–646.
16. Nakamura K, Saku Y, Ibayashi S, Fujishima M. Progressive motor deficits in lacunar infarction. Neurology. 1999;52:29–33.
17. Serena J, Leira R, Castillo J, Pumar JM, Castellanos M, Dávalos A.
Neurological deterioration in acute lacunar infarctions: the role of excitatory and inhibitory neurotransmitters. Stroke. 2001;32:1154–1161.
18. Del Bene A, Palumbo V, Lamassa M, Saia V, Piccardi B, Inzitari D.
Progressive lacunar stroke: review of mechanisms, prognostic features,
and putative treatments. Int J Stroke. 2012;7:321–329.
19. Asdaghi N, Jeerakathil T, Hameed B, Saini M, McCombe JA, Shuaib A, et
al. Oxfordshire community stroke project classification poorly differentiates small cortical and subcortical infarcts. Stroke. 2011;42:2143–2148.
20. Pittock SJ, Meldrum D, Hardiman O, Thornton J, Brennan P, Moroney
JT. The Oxfordshire Community Stroke Project classification: correlation with imaging, associated complications, and prediction of outcome
in acute ischemic stroke. J Stroke Cerebrovasc Dis. 2003;12:1–7.
21. Arboix A, Massons J, García-Eroles L, Targa C, Comes E, Parra O.
Clinical predictors of lacunar syndrome not due to lacunar infarction.
BMC Neurol. 2010;10:31.
22.Arboix A, García-Plata C, García-Eroles L, Massons J, Comes E,
Oliveres M, et al. Clinical study of 99 patients with pure sensory stroke.
J Neurol. 2005;252:156–162.
23. Davis SM, Donnan GA. Why lacunar syndromes are different and important. Stroke. 2004;35:1780–1781.
24. Ringelstein EB, Biniek R, Weiller C, Ammeling B, Nolte PN, Thron A.
Type and extent of hemispheric brain infarctions and clinical outcome
in early and delayed middle cerebral artery recanalization. Neurology.
1992;42:289–298.
25. Davis SM, Donnan GA. Clinical practice. Secondary prevention after
ischemic stroke or transient ischemic attack. N Engl J Med. 2012;366:
1914–1922.
26. Kang DW, Chalela JA, Ezzeddine MA, Warach S. Association of ischemic lesion patterns on early diffusion-weighted imaging with TOAST
stroke subtypes. Arch Neurol. 2003;60:1730–1734.
27. Cho AH, Kang DW, Kwon SU, Kim JS. Is 15 mm size criterion for lacunar infarction still valid? A study on strictly subcortical middle cerebral
artery territory infarction using diffusion-weighted MRI. Cerebrovasc
Dis. 2007;23:14–19.
28. Bang OY, Yeo SH, Yoon JH, Seok JI, Sheen SS, Yoon SR, et al. Clinical MRI
cutoff points for predicting lacunar stroke may not exist: need for a grading
rather than a dichotomizing system. Cerebrovasc Dis. 2007;24:520–529.
29. Lövblad KO, Baird AE, Schlaug G, Benfield A, Siewert B, Voetsch B, et
al. Ischemic lesion volumes in acute stroke by diffusion-weighted magnetic resonance imaging correlate with clinical outcome. Ann Neurol.
1997;42:164–170.
30. Seitz RJ. Stroke recovery: the pyramid in focus. Neurology. 2010;74:
276–277.
31. Ward NS, Cohen LG. Mechanisms underlying recovery of motor function after stroke. Arch Neurol. 2004;61:1844–1848.
32. Duering M, Righart R, Csanadi E, Jouvent E, Hervé D, Chabriat H, et al.
Incident subcortical infarcts induce focal thinning in connected cortical
regions. Neurology. 2012;79:2025–2028.
33. Smith EE, Arboix A. Focal cortical thinning is caused by remote subcortical infarcts: spooky action at a distance. Neurology. 2012;79:2016–2017.
34.Grau-Olivares M, Arboix A, Junqué C, Arenaza-Urquijo EM,
Rovira M, Bartrés-Faz D. Progressive gray matter atrophy in lacunar
patients with vascular mild cognitive impairment. Cerebrovasc Dis.
2010;30:157–166.
35. Suto Y, Nakayasu H, Maeda M, Kusumi M, Kowa H, Awaki E, et al.
Long-term prognosis of patients with large subcortical infarctions. Eur
Neurol. 2009;62:304–310.
36. Tong DC, Yenari MA, Albers GW, O’Brien M, Marks MP, Moseley ME.
Correlation of perfusion- and diffusion-weighted MRI with NIHSS score
in acute (<6.5 hour) ischemic stroke. Neurology. 1998;50:864–870.
37. Thomassen L, Waje-Andreassen U, Broegger J, Naess H. Acute stroke
centre - the changing focus of stroke unit care. The Bergen NORSTROKE
Study. Acta Neurol Scand. 2012;125:410–415.
Downloaded from http://stroke.ahajournals.org/ by guest on October 2, 2016
A Dark Side of Subcortical Diffusion-Weighted Lesions?: Characteristics, Cause, and
Outcome in Large Subcortical Infarction: The Bergen Norwegian Stroke Cooperation
Study
Christopher Elnan Kvistad, Halvor Oygarden, Nicola Logallo, Gunnar Moen, Lars Thomassen,
Ulrike Waje-Andreassen and Halvor Naess
Stroke. 2014;45:2710-2716; originally published online July 10, 2014;
doi: 10.1161/STROKEAHA.114.005781
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright © 2014 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/45/9/2710
Data Supplement (unedited) at:
http://stroke.ahajournals.org/content/suppl/2014/07/10/STROKEAHA.114.005781.DC1.html
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
process is available in the Permissions and Rights Question and Answer document.
Reprints: Information about reprints can be found online at:
http://www.lww.com/reprints
Subscriptions: Information about subscribing to Stroke is online at:
http://stroke.ahajournals.org//subscriptions/
SUPPLEMENTAL MATERIAL
Supplemental table I: Stepwise-backwards multiple regression analysis with LSI vs. LI, CI and
No-LSI as dependent variables and clinical characteristics as independent variables.
OR
95% CI
P
Age
0.99
0.97-1.02
0.552
Sex
0.95
0.44-2.05
0.900
NIHSS on admission
1.14
1.05-1.25
0.004
Time symptom debut – admission
0.99
0.99-1.00
0.893
Diastolic BP on admission
0.99
0.96-1.01
0.220
PACI
4.11
1.96-8.59
<0.001
Symptomatic ICA stenosis ≥70%
8.13
1.18-55.8
0.033
Smoking
0.59
0.26-1.35
0.212
Atrial fibrillation
1.71
0.60-4.79
0.314
Unknown stroke etiology*
3.48
1.68-7.19
<0.001
Age
1.01
0.99-1.03
0.243
Sex
1.04
0.62-1.74
0.888
NIHSS on admission
1.13
1.06-1.20
<0.001
Symptomatic ICA stenosis
7.98
1.92-33.11
0.004
PACI
3.02
1.82-5.01
<0.001
Unknown stroke etiology
3.75
2.28-6.18
<0.001
Age
0.98
0.96-0.99
0.004
Sex
1.01
0.65-1.57
0.966
NIHSS score on admission
1.10
1.04-1.15
<0.001
Prior hypertension
1.37
0.89-2.12
0.157
Systolic BP on admission
1.01
1.01-1.02
0.001
LSI vs LI, N=445
First step (multivariable R2=0.214)
Last step (multivariable R2=0.174)
LSI vs. CI, N= 672
First step (multivariate R2=0.118)
TACI
1.84
0.75-4.49
0.183
LACI
2.66
1.66-4.26
<0.001
Certain time of symptom onset
1.86
1.21-2.85
0.005
Cardioembolic etiology
0.98
0.50-1.90
0.941
Unknown etiology
1.98
1.09-3.59
0.025
Age
0.98
0.96-0.99
0.007
Sex
1.07
0.69-1.64
0.776
NIHSS score on admission
1.11
1.07-1.16
<0.001
Systolic BP on admission
1.01
1.01-1.02
<0.001
LACI
2.56
1.62-4.06
<0.001
Certain time of symptom onset
1.78
1.17-2.72
0.008
Unknown etiology
1.95
1.26-3.00
0.002
Age
1.00
0.99-1.02
0.834
Sex
1.02
0.70-1.51
0.906
NIHSS score on admission
1.05
1.02-1.08
0.003
Prior independency
2.58
1.15-5.78
0.022
Prior hypertension
1.27
0.86-1.88
0.230
Serum leucocytes
0.95
0.88-1.02
0.126
Systolic BP on admission
1.01
1.00-1.01
0.076
LACI
1.91
1.27-2.87
0.002
Unknown etiology
2.73
1.85-4.01
<0.001
Age
1.00
0.99-1.02
0.656
Sex
1.06
0.72-1.55
0.775
NIHSS score on admission
1.04
1.01-1.08
0.005
Prior independency
2.72
1.21-6.08
0.015
Systolic BP on admission
1.01
1.00-1.01
0.042
Last step (multivariate R2=0.115)
LSI vs. no-LSI, N= 1886
First step (multivariate R2=0.060)
Last step (multivariate R2=0.054)
LACI
1.89
1.26-2.84
0.002
Unknown etiology
2.69
1.84-3.94
<0.001
LSI, large subcortical infarction; LI, lacunar infarction; CI, cortical infarction; AI, all infarctions (includes
lacunar infarction, cortical infarction, mixed cortical- and subcortical infarction, cerebellar infarction, brain stem
infarction and infarctions on multiple locations); NIHSS, National Institutes of Health Stroke Scale; BP, blood
pressure; PACI, partial anterior circulation infarct; LACI, lacunar infarct; ICA, internal carotid artery.
*We did not include other etiological variables in this regression analysis due to strong association
between LI and small vessel disease.
Supplemental table II: Stepwise backwards multiple regression analysis with favorable outcome
(mRS 0-1) vs. unfavorable outcome (mRS 2-6) as dependent variable among patients with LSI as
compared to LI, CI and No-LSI.
OR
95% CI
P
Age
0.96
0.94-0.98
<0.001
Sex
0.86
0.54-1.39
0.542
NIHSS score on admission
0.73
0.66-0.81
<0.001
Serum glucose on admission
0.91
0.80-1.03
0.125
Atrial fibrillation
1.15
0.56-2.35
0.708
Smoking
1.47
0.50-2.50
0.156
Prior independency
5.20
1.69-16.07
0.004
Iv treatment with tPA
1.37
0.53-3.55
0.522
LSI
0.46
0.27-0.78
0.004
Age
0.96
0.94-0.98
<0.001
Sex
0.88
0.55-1.40
0.595
NIHSS score on admission
0.74
0.67-0.81
<0.001
Serum glucose on admission
0.90
0.80-1.02
0.096
Prior independency
5.53
1.81-16.90
0.003
LSI
0.43
0.26-0.73
0.002
Age
0.96
0.95-0.98
<0.001
Sex
0.78
0.52-1.16
0.219
NIHSS on admission
0.75
0.70-0.80
<0.001
Serum glucose on admission
0.96
0.89-1.04
0.300
Atrial fibrillation
0.85
0.84-1.32
0.463
Smoking
0.84
0.52-1.32
0.475
LSI vs. LI, N= 445
First step (multivariate pseudo R2=0.232)
Last step (multivariate R2=0.231)
LSI vs. CI, N=672
First step (multivariate R2=0.278)
Prior independency
4.03
1.89-8.61
<0.001
Iv treatment with tPA
1.49
1.89-2.62
0.170
LSI
0.23
0.14-0.38
<0.001
Age
0.96
0.94-0.98
<0.001
Sex
0.81
0.55-1.20
0.297
NIHSS on admission
0.76
0.72-0.81
<0.001
Prior independency
3.78
1.83-7.82
<0.001
LSI
0.23
0.14-0.38
<0.001
Age
0.98
0.97-0.99
<0.001
Sex
0.93
0.74-1.18
0.551
NIHSS score on admission
0.75
0.72-0.78
<0.001
Serum glucose on admission
0.96
0.91-1.00
0.59
Atrial fibrillation
1.04
0.78-1.38
0.795
Smoking
0.94
0.73-1.21
0.629
Prior independency
3.82
2.37-6.17
<0.001
Iv treatment with tPA
1.75
1.24-2.47
0.001
LSI
0.48
0.30-0.75
0.001
Age
0.98
0.98-0.99
<0.001
Sex
0.94
0.75-1.18
0.576
NIHSS score on admission
0.75
0.72-0.78
<0.001
Serum glucose on admission
0.95
0.91-1.00
0.045
Prior independency
3.75
2.33-5.96
<0.001
Iv treatment with tPA
1.82
1.30-2.55
<0.001
LSI
0.48
0.31-0.76
0.002
Last step (multivariate R2=0.276)
LSI vs. No-LSI
N= 1886
First step (multivariate R2=0.214)
Last step (multivariate R2=0.223)
LSI, large subcortical infarction; LI, lacunar infarction; CI, cortical infarction; No-LSI, all infarctions except LSI
(includes LI, CI, mixed cortical- subcortical infarction, cerebellar infarction, brain stem infarction and infarctions
on multiple locations); Iv, intravenous; tPA, tissue plasminogen activator; mRS, modified Rankin Scale.