Change in Perfusion in Acute Nondominant Hemisphere
Stroke May Be Better Estimated by Tests of Hemispatial
Neglect Than by the National Institutes of Health
Stroke Scale
Argye E. Hillis, MD, MA; Robert J. Wityk, MD; Peter B. Barker, DPhil;
John A. Ulatowski, MD, PhD; Michael A. Jacobs, PhD
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Background and Purpose—It has been reported that National Institutes of Health Stroke Scale (NIHSS) scores correlate
poorly with hypoperfused tissue measured by perfusion-weighted imaging (PWI) in nondominant hemisphere stroke.
We conducted 2 studies to determine whether tests of hemispatial neglect provide a better measure of hypoperfusion and
reperfusion than NIHSS in nondominant hemisphere stroke.
Methods—In study 1, 74 patients with acute ischemic, supratentorial stroke were administered the NIHSS, tests of neglect
or aphasia, and diffusion-weighted imaging (DWI) and PWI on day 1 (⬍24 hours from onset) of stroke. Pearson
correlations between volumes of PWI/DWI abnormality and functional tests were calculated. In study 2, 10 patients with
acute, nondominant hemisphere stroke who were candidates for intervention to restore perfusion underwent PWI, DWI,
NIHSS, and a line cancellation test on days 1 and 3. Correlations between change in volumes of PWI/DWI abnormality
and change in functional tests were calculated.
Results—In study 1, in nondominant hemisphere stroke, volume of PWI abnormality correlated significantly with neglect
scores (r⫽0.71; P⬍0.002) but not with NIHSS scores (r⫽0.39; P⫽NS). In dominant hemisphere stroke, volume of PWI
abnormality correlated better with aphasia scores (r⫽0.50; P⫽0.0001) than with NIHSS scores (r⫽0.45; P⫽0.001). In
study 2, change in volume of hypoperfused tissue on PWI correlated with change in line cancellation performance
(r⫽0.83; P⫽0.003) but not with change in NIHSS score (r⫽0.26; P⫽NS).
Conclusions—Tests of hemispatial neglect may better reflect dysfunction and reperfusion than NIHSS for patients with
nondominant hemisphere stroke. (Stroke. 2003;34:2392-2398.)
Key Words: cognition 䡲 magnetic resonance imaging, perfusion-weighted 䡲 reperfusion 䡲 stroke assessment
I
t has recently been demonstrated that there is a low
correlation between National Institutes of Health Stroke
Scale (NIHSS) score and volume of hypoperfusion measured
by MR perfusion-weighted imaging (PWI) in acute nondominant hemisphere ischemic stroke.1 This finding is not surprising because the NIHSS was not designed to measure functions of a large part of the nondominant cortex, which is
prominently involved in spatial attention, integrative or interpretive aspects of cognition, and prosody.2 However, the
result has important implications for acute stroke intervention
trials, which have used either the change in NIHSS score or
change in volume of hypoperfusion as primary outcome
measures on the assumption that both NIHSS score and PWI
abnormality are measures of severity of stroke or volume of
dysfunctional tissue. Some studies have even used NIHSS
score as a substitute for volume of PWI abnormality in
See Editorial Comment, page 2396
estimating the tissue at risk in acute stroke because PWI is not
readily available or standardized.3 There are 2 possible
accounts of the poor correlation between NIHSS score and
volume of hypoperfusion on PWI. First, PWI abnormalities
might not reflect dysfunctional tissue but might reflect
instead benign oligemia.4 Alternatively, the NIHSS might be
a poor estimate of dysfunctional tissue because it is not
sensitive to cognitive functions of the nondominant cortex.
The first explanation is implausible, since several studies
have shown a strong correlation between volume of hypoperfusion on PWI and dysfunction, either using the NIHSS and
volume of hypoperfusion for all strokes (combining dominant
and nondominant hemisphere stroke)5 or using measures of
cognition (language for dominant hemisphere stroke; spatial
attention for nondominant hemisphere stroke6). The second
Received March 13, 2003; final revision received May 13, 2003; accepted June 4, 2003.
From the Departments of Neurology (A.E.H., R.J.W., J.A.U.), Radiology, Division of Neuroradiology (P.B.B., M.A.J.), Anesthesiology and Critical
Care Medicine (J.A.U.), and Neurosurgery (J.A.U.), Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, Md.
Correspondence to Dr Argye E. Hillis, Department of Neurology, Johns Hopkins University School of Medicine, Meyer 5-185, 600 N Wolfe St,
Baltimore, MD 21287. E-mail [email protected]
© 2003 American Heart Association, Inc.
Stroke is available at http://www.strokeaha.org
DOI: 10.1161/01.STR.0000089681.84041.69
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Hillis et al
Changes in Perfusion Estimated by Tests of Neglect
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account—that NIHSS is insensitive to nondominant hemisphere cognitive dysfunction—is plausible, since only 1 item
on the NIHSS pertains to cognitive function of the nondominant hemisphere, whereas several items reflect cognitive
function of the left hemisphere (language) or motor functions.
In this article we report results of 2 studies that evaluate the
possible accounts of the low correlation between NIHSS and
volume of hypoperfusion on PWI in nondominant hemisphere stroke and that evaluate a way to improve measures of
function in acute, nondominant hemisphere stroke. In the first
study we directly test the hypothesis that volume of hypoperfused tissue on PWI correlates more strongly with dysfunction as measured by tests of cognition (language for dominant
hemisphere stroke; spatial attention for nondominant hemisphere stroke) than with dysfunction measured by the NIHSS.
In the second study we evaluate the hypothesis that change in
volume of hypoperfusion on PWI correlates more strongly
with change in scores on a simple test of hemispatial neglect
than with change in NIHSS scores in patients with nondominant hemisphere stroke. We discuss implications of these
findings for measuring effectiveness of therapy in acute
stroke intervention trials.
Subjects and Methods
Study 1: Correlations Between Volume of
Hypoperfusion and NIHSS Score Versus Volume
of Hypoperfusion Cognitive Tests
Study 1: Subjects
A consecutive series of adults with acute, ischemic, supratentorial
stroke, who consented to the study and had none of the following
exclusion criteria, were enrolled. Exclusion criteria were as follows:
contraindication for MRI; allergy to gadolinium; impaired level of
consciousness; hemorrhage on initial CT or MRI; intubation; known
prior history of uncorrected hearing loss, visual loss, or cognitive
impairment; or lack of proficiency in English. Consent was obtained
from each patient and from the closest living relative for patients
with aphasia or neglect resulting from the stroke, with forms and
procedures approved by the Johns Hopkins Institutional Review
Board.
Study 1: Methods
All patients had imaging, including diffusion-weighted imaging
(DWI) and PWI (protocol described below) and a battery of
cognitive tests within 24 hours of onset of stroke symptoms. For
patients with dominant hemisphere stroke symptoms (sensory or
motor deficits affecting the dominant limbs and/or language deficits), a battery of aphasia tests was administered at bedside 1 to 22
(mean⫽10.7) hours after onset. For patients with nondominant
hemisphere stroke symptoms (sensory or motor deficits affecting the
nondominant limbs and/or contralesional hemispatial neglect without aphasia), a battery of tests for hemispatial neglect was administered 1 to 23 (mean⫽11.2) hours after onset. One patient in each
group was tested and imaged within 3 hours; 2 left hemisphere and
1 right hemisphere patients were tested 3 to 6 hours after onset.
These tests are described below.
Aphasia Battery
Tests included the following: (1) oral and written naming of 34
pictured objects; (2) oral naming of 17 objects with tactile input; (3)
oral reading of 34 words and 25 pseudowords; (4) spelling to
dictation of 34 words and 25 pseudowords; (5) spoken word/picture
verification with 17 semantic foils, 17 phonological foils, and 17
correct matches; (6) written word/picture verification with 17 semantic foils, 17 visual foils, and 17 correct matches; and (7) repetition of
34 words and 25 pseudowords. Additionally, each patient was asked
2393
10 yes/no questions, 5 with simple sentence structure and 5 with
reversible sentence structure (eg, Does Monday come after Tuesday?). The battery was scored by total errors divided by total items.
Neglect Battery
Tests included the following: (1) oral reading of 20 words and 5
sentences; (2) line cancellation,7 in which a page of 48 lines is
presented directly in front of the patient, and he or she is instructed
to cross out all of the lines; (3) the bells test,8 in which a page of
figures (eg, bells, horses) is presented with instructions to circle all
of the bells; (4) direct copying of the “Ogden scene”9 (a house, a
fence, and 2 trees); (5) drawing a clock; and (6) a gap detection
task,10 in which patients are asked to detect gaps in 60 circles (20
with left gaps, 20 with right gaps, and 20 with no gap) in 3 different
locations with respect to the body (midsagittal line; 45 degrees to the
right, and 45 degrees to the left). Each segment of the stimulus
figures for copying and each part of the clock were assigned 1 point.
Omission of any point was considered an error. The battery was
scored by total errors divided by total number of items/points.
To obtain norms, we administered these batteries to 46 hospitalized control subjects without any evidence of cognitive impairment
who were awaiting surgical repair of asymptomatic, unruptured
intracerebral aneurysms or awaiting cardiac bypass surgery. These
subjects were comparable in age, education, and sex ratio to the
stroke subjects. Of these 46 control subjects, 22 also had DWI and
PWI before their surgery. Control subjects scored 94.9% correct or
better on each subtest of the batteries. Mean scores for each subtest
ranged from 98.0% (SD⫽3.1) correct in oral reading to 100%
(SD⫽0) correct in tactile naming. Only 1 subject showed any DWI
abnormality (tiny left subcortical infarct, after cardiac catheterization); none showed any PWI abnormality. For subjects and controls
whose highest education was below 10th grade or who reported
premorbid impairment of reading or writing, reading and writing
subtests were not scored. Interjudge reliability in scoring each of the
subtests of each battery was ⬎90% point-to-point percent agreement.
Imaging Protocol
MRI scans, including axial DWI, PWI, T2, and fluid-attenuated
inversion recovery (FLAIR) scans, were obtained on a GE Signa
1.5-T echo-planar imaging– capable system. For DWI, trace images
were obtained with a multislice, isotropic, single-shot echo-planar
imaging sequence, with bmax⫽1000 s/mm2. Imaging parameters were
repetition time/echo time of 10 000/120 ms. For PWI, single-shot,
gradient-echo, echo-planar perfusion images were obtained with 20
mL GdDTPA (gadolinium) bolus power injected at 5 mL/s. Imaging
parameters for PWI were repetition time/echo time of 2000/60 ms;
17 slices were recorded.
To determine total lesion volumes (in cubic centimeters) on DWI
and PWI, a technologist, blinded to the results of NIHSS and
cognitive testing, outlined borders of abnormality on each slice of
DWI or PWI on the computer monitor, then calculated volumes
using Scion Image program (Scion Corporation, 1998). Areas of
abnormality in cubic centimeters on each slice were summed, and the
sum was multiplied by the width of each slice for the volume in cubic
millimeters. Scans were analyzed with the use of 20-color maps to
identify areas with ⬎2.5 seconds of delay relative to the normal side.
Data Analyses
Pearson correlations (with the use of Microstat-II, Ecosoft, 1988)
were calculated for (1) volume of DWI abnormality and NIHSS
score; (2) volume of PWI abnormality and NIHSS score; (3) volume
of DWI abnormality and total score on the cognitive battery; and (4)
volume of PWI abnormality and total score on the cognitive battery.
Study 2: Correlation Between Change in Volume
of Hypoperfusion and Change in Hemispatial
Neglect Score Versus Change in NIHSS Score
Study 1 results indicated that volume of hypoperfused tissue is not
adequately estimated by NIHSS but is well estimated by tests of
hemispatial neglect in patients with nondominant hemisphere stroke.
However, administration of a battery of tests (taking up to 45
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Stroke
October 2003
Demographic Data of Subjects in Study 1
Age
Education
Sex
NIHSS score
Aphasia battery
Dominant Hemisphere Stroke
Nondominant Hemisphere Stroke
23–81 y (mean 64.3)
24–81 y (mean 65.7)
10–20 (mean 14.2)
9–20 (mean 13.8)
52% female
50% female
2–20 (mean 5.8)
1–16 (mean 6.1)
0–100% errors (mean 39.5)
...
Neglect battery
...
0–93% errors (mean 31.9)
DWI abnormality
0.4–111.7 cm3 (mean 18.2)
0.3–110.9 cm3 (mean 16.3)
PWI abnormality
0–341 cm3 (mean 54.9)
0–218 cm3 (mean 72.1)
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minutes) is impractical in the setting of acute stroke intervention
because the effectiveness of most interventions to restore blood flow
depends on rapid initiation. Therefore, in study 2 we evaluated the
hypothesis that change in performance on a single test of hemispatial
neglect that can be administered in ⬍5 minutes is more strongly
correlated with change in volume of hypoperfusion measured with
PWI than is change in NIHSS, in patients with acute nondominant
hemisphere stroke undergoing intervention to improve perfusion.
Study 2: Subjects
The population consisted of a consecutive series of 10 patients who
(1) had stroke affecting the nondominant hemisphere; (2) were
candidates for intervention aimed at restoring perfusion (and enrolled
in an intervention trial or received intervention); and (3) had repeated
MRI, including DWI, FLAIR, and PWI, after intervention or day 3.
Other inclusion and exclusion criteria and consent procedures were
identical to those of study 1.
Study 2: Methods
All patients had MRI and were administered the NIHSS and a single
test of hemispatial neglect at day 1 (within 24 hours of onset, before
intervention) and at day 3 after onset (within 48 hours after initiation
of intervention). Potential interventions to improve perfusion included the following: urgent carotid endarterectomy, carotid stenting, intravenous or intra-arterial thrombolysis, and induced blood
pressure elevation. The last intervention has been described as a
method for improving perfusion in ischemic tissue (which has lost
autoregulation) due to large-vessel stenosis.11–13 None of the patients
received thrombolysis since only 1 presented within 6 hours of onset,
and this patient had other contraindications to thrombolysis. We
selected line cancellation as the measure of hemispatial neglect
because it is easily quantified, rapid to administer (⬍5 minutes), has
a high interjudge reliability in scoring (100% point-to-point percent
agreement by 2 judges on 25 tests), and revealed hemispatial neglect
in 93% of patients who showed neglect on any of the tests in our
neglect battery in study 1.
Imaging methods and analyses were the same as described for
study 1. A technician blinded to the results of line cancellation and
NIHSS scores measured volume of abnormality on DWI and PWI.
Correlations between change in volume of hypoperfusion and change
in NIHSS, as well as change in volume of hypoperfusion and change
in line cancellation performance (defined as percentage of lines
omitted), were calculated. In addition, correlations between change
in volume of infarct/dense ischemia (defined as bright on DWI and
dark on apparent diffusion coefficient maps) and change in NIHSS,
as well as change in volume of infarct/dense ischemia and change in
line cancellation performance, were calculated.
hemisphere versus nondominant hemisphere stroke with respect to age, education, sex, NIHSS scores, scores on the
aphasia or neglect battery, volume of DWI abnormality, or
volume of PWI abnormality (Table).
For patients with nondominant hemisphere stroke, there
was a significant correlation between volume of PWI abnormality and neglect battery scores (r⫽0.71; P⬍0.002) but not
a significant correlation between volume of PWI abnormality
and NIHSS scores (r⫽0.39; P⫽NS). DWI abnormality correlated with neither neglect scores (r⫽0.21; P⫽NS) nor
NIHSS (r⫽⫺0.09; P⫽NS). For patients with dominant hemisphere stroke, there was a higher correlation between volume
of PWI abnormality and aphasia battery scores (r⫽0.50;
P⫽0.0001) than between volume of PWI abnormality and
NIHSS scores (r⫽0.45; P⫽0.001). DWI abnormality correlated with neither language scores (r⫽0.16; P⫽NS) nor
NIHSS scores (r⫽0.18; P⫽NS).
Examples of scans of patients with various degrees of
hemispatial neglect are shown in Figure 1.
Study 2
Of the 10 patients, 9 were right-handed and had right
hemisphere strokes; 1 was left-handed and had a left hemisphere stroke with right neglect and no aphasia (with normal
performance on our aphasia battery). Fifty percent were
female. Mean initial NIHSS score was 9 (range, 1 to 16).
Mean initial score on the line cancellation test was 55.5%
Results
Study 1
A total of 74 patients (48 dominant, 26 nondominant hemisphere), all with anterior circulation stroke, enrolled in the
study. Demographic data are given in the Table. There were
no significant differences between patients with dominant
Figure 1. Scans and neglect tests done ⬍24 hours from onset
showing 3 levels of severity of hypoperfusion and hemispatial
neglect.
Hillis et al
Changes in Perfusion Estimated by Tests of Neglect
Figure 2. Examples of patients who showed reduced volume of
hypoperfusion and reduced error rates on line cancellation after
intervention.
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
errors (range, 12% to 93%). Mean volume of DWI abnormality was 8.9 cm3 (range, 3 to 31 cm3). Mean volume of PWI
abnormality was 156 cm3 (range, 55 to 284 cm3). All patients
had a large DWI-PWI mismatch and were considered candidates for intervention to improve perfusion. All patients had
stenosis or occlusion of the middle cerebral artery and/or
internal carotid artery on the symptomatic side, confirmed
with MR angiogram or conventional angiogram. Intervention
consisted of urgent endarterectomy (1 patient), carotid stenting (1 patient), and induced blood pressure elevation (5
patients). An additional 3 patients were randomized to conventional management (ie, served as controls) in a trial of
induced blood pressure elevation; these 3 patients and 3 of the
patients treated with induced blood pressure elevation participated in that study.13 Therefore, patients with various degrees of reperfusion were included.
Mean change in NIHSS score was ⫺1.7 (range, ⫺5 to 0).
Mean change in line cancellation score was ⫺14.3 (range,
⫺39.6 to ⫹14.6). Mean change in DWI abnormality was 4.3
cm3 (range, ⫺4 to 32 cm3). Mean change in PWI abnormality
was ⫺70.2 cm3 (range, ⫺209 to 0 cm3). There was a
significant correlation between change in volume of hypoperfused tissue on PWI and change in line cancellation performance (r⫽0.83; r2⫽0.69; P⫽0.003). In contrast, there was
not a significant correlation between change in volume of
hypoperfusion and change in NIHSS score (r⫽0.26; r2⫽0.07;
P⫽NS). There was also not a significant correlation between
change in volume of infarct/densely ischemic tissue on DWI
and change in either line cancellation performance (r⫽0.10;
r2⫽0.01; P⫽NS) or NIHSS score (r⫽⫺0.48; r2⫽0.23;
P⫽NS) in these patients, since none showed substantial
change in DWI abnormality.
Examples of MR scans before and after intervention in
patients with hemispatial neglect before intervention are
shown in Figure 2. It is not the case that all patients improved
in both perfusion and line cancellation. The case in Figure 3
illustrates MR scans and line cancellation tests in patients
who did not significantly improve in either line cancellation
or volume of hypoperfusion.
Discussion
Animal studies of acute stroke intervention have generally
used final infarct size or imaging characteristics as the final
2395
Figure 3. Example of patient who showed little change in volume of hypoperfusion and little change in line cancellation
performance.
outcome measure. In contrast, in human acute stroke intervention trials, outcome has most often been measured by the
NIHSS score (often along with the Glasgow Outcome Scale,
Rankin Scale, and/or Barthel Index) because function is
considered a more important outcome than imaging characteristics or because imaging is less standardized or less
commonly available. However, none of these functional
scales is sensitive to degrees of hemispatial neglect, which is
among the most disabling impairments in patients with
nondominant hemisphere stroke (see Azouvi et al14 for
review of assessment and outcome of neglect). Furthermore,
although changes in these measures of function such as
NIHSS have been assumed to reflect the volume of “salvaged” tissue, results of the present study challenge this
assumption. Consistent with a previous study,1 we found no
significant correlation between the NIHSS score and volume
of hypoperfused tissue on PWI for patients with nondominant
hemisphere stroke, although we did find a strong correlation
between volume of hypoperfused tissue estimated by PWI
and cognitive performance in both dominant and nondominant hemisphere stroke. Results of study 1 suggest that
volume of hypoperfused tissue may reflect dysfunctional
tissue (as measured by aphasia or neglect tests or by NIHSS
for dominant hemisphere stroke), but NIHSS does not reflect
dysfunctional tissue in patients with nondominant hemisphere
stroke. This conclusion is further corroborated by the results
of study 2, which demonstrated that change in volume of
hypoperfused tissue was associated with change in a test of
hemispatial neglect but not associated with change in NIHSS
score.
One caveat in our conclusion from study 2 is that patients
were selected for intervention to restore perfusion on the
basis of a large diffusion-perfusion mismatch. Therefore, all
of these patients had a large area of cortical hypoperfusion
associated with hemispatial neglect. Although hemispatial
neglect has been well described after subcortical stroke (see
Karnath et al15 for review), a recent study indicated that
neglect after nondominant subcortical stroke is due to cortical
hypoperfusion.10 Thus, the test of line cancellation would be
a poor measure of the volume of dysfunctional tissue in
patients with nondominant subcortical stroke without cortical
hypoperfusion because change in volume of subcortical tissue
dysfunction might not be reflected at all in line cancellation
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October 2003
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performance. In patients with strictly subcortical stroke,
NIHSS may be an adequate measure of tissue dysfunction,
although this hypothesis has not yet been tested. A second
caveat is that study 2 included a small number of patients,
indicating the need to confirm results with a larger
population.
The implication of our results is straightforward. The
NIHSS score alone does not provide a good estimate of the
volume of hypoperfused tissue or change in hypoperfused
tissue in nondominant stroke affecting the cortex. One previous group tried to improve the “lateralization bias” (more
points for dominant hemisphere stroke) and to improve the
reliability and validity of the NIHSS by dropping items
concerning facial weakness and dysarthria.16 While this
change may improve interjudge reliability, the authors’ claim
that omitting the dysarthria item improves the lateralization
bias is not supported because dysarthria occurs after stroke in
either hemisphere or more commonly after brain stem stroke
or bilateral strokes. The implication from the present study is
that volume of tissue with restored blood flow in patients with
nondominant hemisphere stroke in acute intervention trials
would be better measured either with a combination of
NIHSS and some measure of hemispatial neglect or with
imaging (eg, PWI, in conjunction with DWI and FLAIR
images). We have demonstrated that a very simple, bedside
test of hemispatial neglect (line cancellation), which takes ⬍5
minutes to administer, may be a good estimate of volume of
hypoperfusion, or dysfunctional tissue, in patients with acute
nondominant stroke affecting cortical perfusion.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
Acknowledgments
This study was supported by a National Institutes of Health grant
(RO1 DC05375) and by a grant from the Charles A. Dana Foundation to Dr Hillis.
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Editorial Comment
Measurement of Cognitive Deficits in Acute Stroke
Whereas diffusion-weighted imaging (DWI) identifies areas
of metabolic failure and cellular injury that are often, but not
invariably, irreversible,1 perfusion-weighted imaging (PWI)
depicts areas of hypoperfusion that, when not matched by a
diffusion abnormality, constitute the potentially reversible
ischemic penumbra.2 Early neurological deficits correlate
with core and penumbral lesion volume rather than with the
diffusion abnormality.3 These new imaging techniques are
powerful tools that provide insights into the pathophysiology
of the deficits and the effects of therapeutic interventions in
patients with acute stroke.
Earlier SPECT observations showed that patients with
subcortical stroke and aphasia or neglect had decreased
cortical perfusion that was attributed to the interruption of
neural connections (diaschisis).4 Using neuropsychological
tests and PWI, however, Hillis and colleagues have shown
that patients with subcortical strokes have aphasia and neglect
because of the cortical hypoperfusion,5 and that these deficits
improve when blood flow to the cortex is restored.5,6 In this
issue of Stroke, Hillis et al demonstrate that a battery of
neurobehavioral tests that assess language and attention
correlates well with the volume of hypoperfused cortex but
that the National Institute of Health Stroke Scale (NIHSS)
score correlates poorly when the left hemisphere is involved
and not at all when right hemisphere is injured. Neither
neurobehavioral nor NIHSS scores correlated with DWI
Hillis et al
Changes in Perfusion Estimated by Tests of Neglect
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abnormalities, regardless of which hemisphere was affected.7
Furthermore, in a second experiment, they found that among
patients with right-sided stroke, treatment-induced changes in
perfusion correlate with changes in performance on the line
cancellation task but not with changes in the NIHSS score.7
Attention depends on a complex neuroanatomically distributed modular network8 that includes the dorsolateral prefrontal lobes, the posterior and superior temporal and inferior
parietal lobes, the cingulate gyrus, and portions of the
diencephalic and mesencephalic reticular activating system.
Lesions anywhere in this network, particularly— but not
exclusively—in the right hemisphere, can lead to attention
abnormalities including extinction, hemispatial neglect, personal neglect, and anosognosia. Attention deficits are found
in 20% to 40% of patients 3 months after a stroke.9,10 While
these deficits do not always precisely localize the lesion, it is
important to identify them because they are disabling and
negatively impact rehabilitation. They are, however, rarely
elicited or recorded by neurologists in the acute stage,
particularly when a standardized scale is not used.11
The findings reported in this issue by Hillis and colleagues
highlight some issues regarding the NIHSS that have been
previously identified.12,13 This scale is used to select acute
stroke patients for treatment with pharmacological and mechanical agents, and is a measure of stroke severity in many
prospective stroke databases. The scale, however, is biased
toward left hemisphere strokes, since 7 out of 42 possible
points are assigned to language dysfunction while only 2 are
given for neglect. As a result, for a given NIHSS score the
volume of acute diffusion-weighted (DWI) abnormality13 and
of infarction on CT12 is larger when the stroke is in the right,
particularly if the deficits are mild.13 This bias has significant
implications. Patients with low NIHSS scores are seldom
treated with tissue plasminogen activator, even though one
third of the untreated patients die or are dependent at
discharge.14 In addition, higher NIHSS score and stroke
volume are associated with worse outcomes,15,16 and when
strokes of similar size in both hemispheres are compared,
those in the right lead to worse outcomes.17
Hillis et al demonstrate that a battery of cognitive tests that
takes about 45 minutes to administer correlates with PWI
abnormalities.5–7 We need a shorter instrument for use in
clinical care and research in the acute setting. Hillis et al
chose the line cancellation task for the second experiment for
its sensitivity and reliability. However, different tests assess
separate components of the neglect syndrome, and patients
may perform well on one test but not on the other.18 Binder
and colleagues did not find a correlation between the scores
in the line bisection and the letter cancellation tasks.19
Perhaps a measure that combines elements of both tests, such
as one recently proposed by Na and coworkers, will be
useful.20 This test consists of horizontally aligned strings of
characters and the subject’s task is to mark a target character
that is at, or closest to, the true midpoint of the simulated line.
The sensitivity and specificity of this task in the setting of
acute stroke, however, still need to be established.
More than 60% of patients have deficits in at least one
cognitive domain 3 months after a stroke,10 yet cognitive
disorders are often either overlooked or underestimated in the
2397
assessment of acute stroke. Clinical trials inadequately assess
cognitive status as an outcome measure. In their second
experiment, Hillis and colleagues demonstrate the value of
using cognitive outcomes—the treatment associated change
in perfusion correlated with changes in performance of line
cancellation task but not with changes in the NIHSS.7 Thus,
there is a need for a cognitive scale that can be used in
conjunction with the NIHSS both to select patients for acute
stroke treatment and to be used as baseline and outcome
measure in clinical trials. Such a scale must allow prompt
evaluation of the domains that are most often affected by
stroke and must be simple to administer by physicians who
are not familiar with neurobehavioral testing. Like the NIHSS
it should provide an overall numeric score, but should also
provide subscores that can be used to track changes in
individual domains over time. The scale can have a brief
multicognitive domain screening section that can be applied
in a few minutes before treatment, and more detailed components to address domains where the patient performed
abnormally. Data such as those presented by Hillis et al in this
issue should be the basis for such a scale.
José G. Merino, MD, MPhil, Guest Editor
Department of Neurology
University of Florida College of Medicine
Jacksonville, Florida
Kenneth M. Heilman, MD, Guest Editor
Department of Neurology
University of Florida College of Medicine
Veterans Affairs Medical Center
Gainesville, Florida
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Editorial Comment−−Measurement of Cognitive Deficits in Acute Stroke
José G. Merino and Kenneth M. Heilman
Downloaded from http://stroke.ahajournals.org/ by guest on June 17, 2017
Stroke. 2003;34:2396-2398; originally published online September 18, 2003;
doi: 10.1161/01.STR.0000094661.43891.F9
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