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CME Hemispatial neglect
Subtypes, neuroanatomy, and disability
L.J. Buxbaum, PsyD; M.K. Ferraro, PhD; T. Veramonti, BA; A. Farne, PhD; J. Whyte, MD, PhD;
E. Ladavas, PhD; F. Frassinetti, MD; and H.B. Coslett, MD
Abstract—Objective: To assess the relative frequency of occurrence of motor, perceptual, peripersonal, and personal
neglect subtypes, the association of neglect and other related deficits (e.g., deficient nonlateralized attention, anosognosia),
and the neuroanatomic substrates of neglect in patients with right hemisphere stroke in rehabilitation settings. Methods:
The authors assessed 166 rehabilitation inpatients and outpatients with right hemisphere stroke with measures of neglect
and neglect subtypes, attention, motor and sensory function, functional disability, and family burden. Detailed lesion
analyses were also performed. Results: Neglect was present in 48% of right hemisphere stroke patients. Patients with
neglect had more motor impairment, sensory dysfunction, visual extinction, basic (nonlateralized) attention deficit, and
anosognosia than did patients without neglect. Personal neglect occurred in 1% and peripersonal neglect in 27%, motor
neglect in 17%, and perceptual neglect in 21%. Neglect severity predicted scores on the Functional Independence Measure
and Family Burden Questionnaire more accurately than did number of lesioned regions. Conclusions: The neglect
syndrome per se, rather than overall stroke severity, predicts poor outcome in right hemisphere stroke. Dissociations
between tasks assessing neglect subtypes support the existence of these subtypes. Finally, neglect results from lesions at
various loci within a distributed system mediating several aspects of attention and spatiomotor performance.
NEUROLOGY 2004;62:749 –756
Hemispatial neglect is defined as a failure to attend
to the contralesional side of space. Its reported fre-
quency varies widely from 13% to 81% of patients
who have had right hemisphere stroke.
1
Patients
with neglect are more impaired than patients with-
out neglect on measures of impairment and disabil-
ity, and have longer rehabilitation hospitalizations.
2
Neglect has been reported consequent to lesions to
the right temporo-parietal-occipital (TPO) junction,
parietal lobe, frontal lobe, thalamus, and basal gan-
glia,
3
but it has been proposed that lesions to the
superior temporal lobe and associated subcortical
structures are crucial to its occurrence.
4
Neglect may differentially affect attention and
perception versus intention and action.
3,5,6
Thus,
some patients with neglect may exhibit directional
hypokinesia for actions into and toward contrale-
sional hemispace, whereas others may fail to re-
spond to stimuli on the left of the eyes, head, or body,
irrespective of the required motor response. Contro-
versy exists as to whether the motor and perceptual
subtypes may be associated with anterior versus pos-
terior lesions.
5,7
Neglect may affect the contralesional
body (personal neglect), contralesional near space
within reaching distance (peripersonal neglect), or
space beyond reaching distance (extrapersonal ne-
glect).
8,9
Nonlateralized deficits in attention may be
prominent,
10
and an important influence on its severity
and persistence.
11
Neglect patients may be severely im-
paired in detecting targets in both hemispaces,
12
and
may perform poorly on simple tone-counting tasks
measuring nonlateralized attention.
13
Somatosensory, visual field, and motor deficits are
all more frequent after right than left hemisphere
stroke, suggesting that primary sensory deficits may
be augmented by neglect.
14
Anosognosia, or unaware-
ness of deficit, is also more frequent after right than
left hemisphere lesions, and may compound the dis-
ability deriving from the neglect itself.
15
Given this diversity, an impediment to progress in
neglect treatment has been difficulty defining the
subject population. Recent large-scale studies of ne-
glect
16
have described the frequency of occurrence of
neglect, its clinical course, and its neuroanatomic
correlates. To our knowledge, there have been no
large studies assessing the frequency of neglect sub-
types or deficits in nonlateralized attention. These
factors may have implications for the level of pa-
tients’ disability, as well as for development of treat-
ment studies targeted to the pattern of impairment.
Additional material related to this article can be found on the Neurology
Web site. Go to www.neurology.org and scroll down the Table of Con-
tents for the March 9 issue to find the title link for this article.
From Moss Rehabilitation Research Institute (Drs. Buxbaum, Ferraro, Whyte, and Coslett, and T. Veramonti), Philadelphia; Thomas Jefferson University
(Drs. Buxbaum and Whyte), Philadelphia; Centro di Neuroscienze Cognitive (Drs. Farne, Ladavas, and Frassinetti), Dipartimento di Psicologia
dell’Universita di Bologna, Italy; and University of Pennsylvania (Dr. Coslett), Philadelphia. T. Veramonti is currently affiliated with the University of
Houston, TX.
Supported by a grant from the James S. McDonnell Foundation (L.J.B.).
Received July 12, 2002. Accepted in final form November 13, 2003.
Address correspondence and reprint requests to Dr. Laurel Buxbaum, Moss Rehabilitation Research Institute, Korman 213, 1200 W. Tabor Rd., Philadelphia,
PA 19141; e-mail: Lbuxbaum@einstein.edu
Copyright © 2004 by AAN Enterprises, Inc. 749
Before designing such studies, it is important to as-
sess the frequency with which the putative subtypes
and co-occurring deficits can be detected in a rehabil-
itation population with right hemisphere stroke.
Methods. Patients. We studied 166 patients who had right
hemisphere stroke. Patients were recruited from inpatient and
outpatient stroke services of MossRehab, Bryn Mawr Rehab, and
Magee Rehabilitation Hospitals in the greater Philadelphia area
in the United States, as well as the National Institute for Re-
search and Care in Aging Fraticini Glicini and San Camillo Hos-
pitals in Italy. Patients were considered eligible for the study if
they had sustained a hemorrhagic, embolic, or thrombotic right
hemisphere stroke within the previous 3 years. See E-Methods at
www.neurology.org for subject criteria and testing schedules. Of
an original 623 charts (503 American, 120 Italian) of right hemi-
sphere stroke patients screened, 268 (188 American, 80 Italian)
met study criteria, 257 (177 American, 80 Italian) were ap-
proached for consent to participate, and 166 (96 American, 70
Italian) gave informed consent. There were 86 patients with acute
lesions and 80 patients with chronic lesions (more than 3 months,
less than 3 years post right hemisphere stroke). Table 1 provides
demographic information for all subjects.
Italian and American patients did not differ in age (acute: t ⫽
⫺1.6, p⫽0.12; chronic: t ⫽1.4, p⫽0.16), but Italian patients had
fewer years of education than American subjects (acute: t ⫽11.2,
p⬍0.0001; chronic: t ⫽6.2, p⬍0.0001). Acute American patients
had had strokes more recently than acute Italian patients (t ⫽
⫺5.5, p⬍0.0001), likely reflecting differences in health care deliv-
ery, but stroke recency was equivalent in the American and Ital-
ian chronic groups (t ⫽⫺1.2, p⫽0.21). There proved to be no
difference in the proportion of patients with operationally defined
neglect in the Italian and American populations in either the
acute (
2
⫽2.5, p⫽0.15) or chronic group (
2
⫽0.005, p⬎0.99).
There also proved to be no difference between the American and
Italian acute patients in clinical severity as measured by the
Functional Independence Measure (FIM, 1996; FIM Physical
Scale t ⫽⫺0.94, p⫽0.35; FIM Cognitive Scale t ⫽⫺0.82, p⫽
0.41). There were insufficient FIM data from chronic patients to
perform a similar comparison. The reported analyses combined
American and Italian patients into a single group unless other-
wise noted.
Test battery. Patients were assessed with a comprehensive
battery of tests. They were seated in a quiet, dedicated testing
room at a desk. The examiner sat beside them to the right. Exam-
iners were trained to administer all tests in a standardized man-
ner. Patients were instructed with simple directions, which were
read to them aloud from a standard script. Order of test adminis-
tration was randomized.
Clinical tests of neglect. Five tests comprised the clinical ne-
glect battery: The Bells Test17 and four subtests of the Behavioral
Inattention Test (BIT)18: Letter Cancellation, Picture Scanning,
Menu Reading, and Line Bisection. See E-Methods at www.
neurology.org for test descriptions and scoring procedures.
Motor examination. Right and left grip strength was mea-
sured with a hand-held dynamometer. Three trials were per-
formed with each hand at midline and the mean grip strength (kg)
was recorded.
Active range of motion of the left shoulder, elbow, wrist, and
fingers was measured using a standard 12-inch goniometer.
Range of motion of the index finger was assessed with a 6-inch
finger goniometer.
Sensory examination. Visual fields and visual extinction were
assessed with presentation of four unilateral right, four unilateral
left, and four bilateral visual stimuli (slight finger movement) in
randomized order. Head and body were aligned.
Tactile sensation and tactile extinction were assessed with pre-
sentation of a light tactile left, right, or bilateral stimulus on the
dorsum of the hands (n ⫽4 each).
See E-Methods at www.neurology.org for scoring information.
Sustained and divided attention. The Sustained Attention to
Response Test (SART13) was used to assess sustained attention
and response inhibition.
The Dual Task test was used to measure simple response time
with and without a secondary task load.19 See E-Methods at www.
neurology.org for test descriptions and scoring information.
Motor and perceptual neglect. Because most common paper
and pencil tests of neglect confound the need to perceive left sided
stimuli with the requirement to respond (e.g., cancel them), we
developed two tasks that would separate these factors. The Later-
alized Target and Lateralized Response Tests20 measured re-
sponse latencies in two different stimulus/response conditions. See
E-Methods at www.neurology.org for test description and scoring
information.
Personal and peripersonal neglect. The determination of
peripersonal neglect was based on performance below a cutoff
score on any one of the five clinical paper-and-pencil tests listed
above. The cutoff scores were as follows: Bells Test (L ⫺R differ-
ence) ⫽⫺4; Letter Cancellation (L ⫺R difference) ⫽⫺4; Menu
Reading (L ⫺R difference) ⫽⫺3; Picture Scanning (L ⫺R%
difference) ⫽⫺20%; Line Bisection (mean deviation, mm) ⫽13.
See E-Methods: Determination of cut-off scores at www.neurology.
org for more details.
Personal neglect was assessed by placing six cotton balls on a
blindfolded participant’s left side at shoulder, chest, elbow, fore-
arm, wrist, and hip (for a similar test, see reference 21). Upon
removal of the blindfold, the participant was instructed to locate
and remove the cotton balls. The number of detected targets was
tallied (0 to 6).
Anosognosia. At the end of each test session, a five-question
Anosognosia Questionnaire (adapted from reference 22) was ad-
ministered that addressed sensorimotor impairment and general
awareness of deficit. See E-Methods at www.neurology.org for test
description and scoring information.
Clinical severity. The 18-item FIM23 was administered to
acute inpatients at admission and discharge by clinicians trained
and certified according to procedures of the Uniform Data System.
See E-Methods at www.neurology.org for test description and
scoring information.
Caregiver ratings of burden. The families of all chronic pa-
tients were administered the Family Burden Questionnaire (FBQ;
adapted from the Questionnaire on Resources and Stress24). This
is a 10-point true/false questionnaire, which is designed to assess
stress placed on the family of the stroke patient (e.g., “_______”is
hard to live with; “_______”doesn’t do as much as s/he should do).
Lesion analyses. Clinical neuroimaging scans were available
for 156 of the 166 patients (94%). Scans for the majority (83%) of
patients were CT; the remainder (17%) were T2/proton density
MRI. Scans were interpreted by the project neurologists (H.B.C.
and F.F.) who were naïve to patients’identities and clinical pre-
sentations. Patients with left hemisphere lesions larger than
Table 1 Demographic information
Characteristics
American acute,
n⫽62 Italian acute, n ⫽24
American chronic,
n⫽34 Italian chronic, n ⫽46
Mean (SD) Range Mean (SD) Range Mean (SD) Range Mean (SD) Range
Age, y 66.2 (12) 37–89 70.5 (10.4) 50–88 66.6 (11.9) 43–89 63.6 (11.7) 33–82
Years of Education 12.9 (2.9) 5–20 4.9 (3.2) 1–18 12.9 (3.9) 5–20 7.5 (4) 3–19
Days post onset 16.8 (6.8) 5–37 26.2 (7.8) 15–41 303.0 (169.5) 94–700 376.3 (304.7) 60–1272
No. men/no. women 29/33 12/12 20/14 27/19
750 NEUROLOGY 62 March (1 of 2) 2004
small lacunes were to be excluded at this stage; however, there
were none. Lesion location was coded using 37 regions adopted
from template A18 or A20 (depending on slice angle) of Damasio
and Damasio.25 Eight subcortical regions in the internal capsule,
thalamus, and basal ganglia not appearing on the template were
also coded. For the purpose of some of the analyses to be reported
(see below), these were subsequently collapsed into 10 regions of
interest: 1. cingulate and orbital frontal; 2. prefrontal, periven-
tricular, and deep white matter; 3. sensory-motor; 4. superior and
middle temporal; 5. inferior temporal/mesial temporal; 6. inferior
parietal; 7. superior parietal; 8. occipital; 9. basal ganglia (cau-
date, putamen, globus pallidus); 10. thalamus and internal cap-
sule (including but not limited to anterior limb).
Data analysis. See E-Data analysis at www.neurology.org for
information on data analysis.
Results. Frequency of neglect in the study popula-
tion. Forty-two (49%) of the acute and 38 (47%) of the
chronic patients exhibited neglect on at least one of the five
clinical tests. For acute patients, determination of motor, per-
ceptual, personal, and peripersonal neglect was based upon
data from the last testing session. Hereafter, acute patients
meeting the criteria for neglect will be identified as A⫹, acute
patients without neglect as A-, chronic patients with neglect
as C⫹, and chronic patients without neglect as C-.
Table 2 shows patients’scores on all five clinical tests of
neglect (Bells Test, Letter Cancellation, Picture Scanning,
Menu Reading, Line Bisection). All scores were correlated
(0.22 ⬍r⬍0.69; all p⬍0.05). Consequently, for each
patient we calculated the percentile rank on each of the
five clinical tests, and then averaged this rank. The result-
ant score (hereafter, average neglect percentile) was used
in several of the analyses reported.
Additional characteristics of the neglect syndrome. Motor
function. Range of motion (ROM) scores from all joints were
highly correlated by Spearman correlation coefficient (rho ⬎
0.85, p⬍0.0001 for all analyses). Consequently, ROM scores
were averaged, and a percentile score computed (average
ROM percentile). There was a moderate correlation between
the average neglect percentile and average ROM percentile
scores (r ⫽0.45, p⬍0.0001), indicating that patients with
more severe neglect were likely to have more severe ROM
impairment.
See E-Results: Motor function at www.neurology.org for
further detail.
Sensory function. Table 2 presents results of visual
and tactile sensory testing. To summarize, visual and tac-
tile sensory loss is more likely to occur in patients with
neglect than in those without neglect. Visual extinction is
also associated with neglect, but only in the acute popula-
tion. Tactile extinction is not strongly associated with ne-
glect. The association of visual extinction and neglect is
consistent with previous findings.
26
Anosognosia. Mean scores on the anosognosia test dif-
fered by Mann Whitney tests for the A⫹and A- groups
(A⫹mean ⫽2.0, SD 2.0; A- mean ⫽0.3, SD 0.8, U ⫽⫺4.0,
p⬍0.0001) as well as for the C⫹and C- groups (C⫹
mean ⫽1.6, SD 1.7; C- mean ⫽0.1, SD 0.4, U ⫽⫺4.5, p⬍
0.0001). Patients with neglect had less awareness of deficit
than did patients without neglect. One limitation of these
Table 3 Frequency of neglect subtypes
Tests Acute Chronic
Completed motor and perceptual tests 71 76
Both motor and perceptual neglect 2 (3) 8 (11)
Motor neglect only 12 (17) 8 (11)
Perceptual neglect only 15 (21) 10 (13)
Neither motor nor perceptual neglect 42 (59) 50 (65)
Completed personal and peripersonal tests 84 80
Both personal and peripersonal neglect 15 (18) 11 (14)
Personal neglect only 1 (1) 1 (1)
Peripersonal neglect only 23 (27) 24 (30)
Neither personal nor peripersonal
neglect
45 (53) 44 (55)
Values are n (%).
Table 2 Scores of acute and chronic neglect and non-neglect patients on tests of “clinical” neglect
Test
A⫹, Mean (SD)
n⫽42
A⫺, Mean (SD)
n⫽44
C⫹, Mean (SD)
n⫽38
C⫺, Mean (SD)
n⫽42
Bell Cancellation, L ⫺R difference ⫺4.9 (4.6) ⫺0.1 (1.6) ⫺4.9 (4.3) ⫺0.3 (1.3)
Letter Cancellation, L ⫺R difference ⫺2.7 (4.9) 0.6 (1.5) ⫺4.3 (5.9) 0.6 (1.5)
Menu Reading, L ⫺R difference ⫺2.6 (3.9) ⫺0.1 (0.3) ⫺2.8 (4.2) 0 (0)
Picture Identification, L ⫺R percent
difference
⫺29.7 (32.1) 0.7 (4.5) ⫺24 (35.2) 1.1 (4.9)
Line Bisection, deviation, mm 9.7 (21) 0.9 (6.4) 18 (20.4) ⫺0.4 (5.4)
N(%ofgp) N(%ofgp) N(%ofgp) N(%ofgp)
Field Defects 12 (30) 0 (0)†15 (40) 1 (2)†
Visual Extinction 14 (34) 4 (9)* 9 (24) 6 (14) NS
Tactile Sensory Loss 16 (41) 5 (11)* 15 (40) 1 (2)†
Tactile Extinction 9 (23) 7 (16) NS 13 (34) 12 (29) NS
Significance of
2
:*p⬍0.01; †p⬍0.001; NS ⫽not significant.
A⫹⫽acute patients with neglect; A⫺⫽acute patients without neglect; C⫹⫽chronic patients with neglect; C⫺⫽chronic patients
without neglect.
March (1 of 2) 2004 NEUROLOGY 62 751
data, however, is that there is less opportunity for under-
estimation of actual disability in patients with less
disability.
27
Subtypes of neglect. Table 3 shows the data from sub-
jects who completed testing for both perceptual and motor
neglect (lateralized target, lateralized response), as well as
from a partially overlapping group of subjects who com-
pleted testing for personal and peripersonal neglect (clini-
cal neglect tests, fluff test). These data indicate that
combinations of subtype deficits appear in the population,
with the exception of isolated personal neglect, which is
relatively uncommon, at least as assessed by the single
measure employed here (see Discussion for additional com-
ment). We also assessed the number of patients exhibiting
a neglect subtype (⬍20th percentile on relevant task)
whose score was above average (⬎50th percentile) on the
contrasting relevant task. See E-Methods: Subtypes at
www.neurology.org for details. Even with this more con-
servative estimate, there were still patients who could be
characterized as exhibiting a pure neglect subtype.
In addition, we looked at the numbers of subtypes tasks
on which patients were impaired, and thus the degree to
which patients could be characterized as exhibiting a com-
plex combination of deficits. As shown in table 4, a pattern
of impairment on multiple tasks was quite common.
Relationship of lateralized and nonlateralized attention
deficits. Table E-5 (available at www.neurology.org)
shows patients’scores on the Dual Task tests and on the
SART, along with normative data from 20 healthy adult
participants we recently reported
28
(mean age 62 years, SD
11; mean education 13.4 years, SD 2.7; 8 men and 12
women).
Previous investigators have suggested that deficits in
basic attention and sensorimotor response speed are a
prominent component of the neglect syndrome.
29
We as-
sessed that hypothesis in an analysis that can be viewed
online (see E-Results: Attention and sensorimotor response
speed at www.neurology.org). The data support previous
findings suggesting that neglect is associated with deficits
in sensorimotor response speed
10
and nonexecutive aspects
of attention (i.e., what has been called “posterior atten-
tion”
30
). These capacities have been linked to the attention
system of the right hemisphere, and in particular the right
parietal lobe.
31
On the other hand, neglect is not associated
with executive capacities involved in performing under
dual task load and in inhibiting responses to infrequent
targets. These functions are frequently attributed to fron-
tal lobe structures.
30
Clinical implications of the neglect syndrome. A dis-
cussion of FIM and caregiver burden data may be viewed
online (see E-Results: Clinical implications of the neglect
syndrome at www.neurology.org). These data indicate that
Figure 1. Proportion of acute (top) and chronic (bottom)
patients with neglect (black bars) and without neglect
(white bars) having lesions in defined neuroanatomic re-
gions of interest. Asterisks mark significant differences.
C i n/O F ⫽cingulate, orbito-frontal; PF/WM ⫽prefrontal,
periventricular white matter; SM ⫽sensory-motor;
S T/M T ⫽superior temporal, middle temporal; IT/MesT ⫽
inferior temporal/mesial temporal; IP ⫽inferior parietal;
SP ⫽superior parietal; O ⫽occipital; BG ⫽basal gan-
glia; Th/IC ⫽thalamus, internal capsule.
Table 4 Patterns of performance on the measures of neglect
subtypes, ranked by numbers of subjects
Peripersonal Personal Perceptual Motor Acute Chronic Total
⫹⫺⫹⫺10 12 22
⫹⫺⫺⫺91019
⫹⫺⫺⫹12 6 18
⫹⫹⫹⫺6410
⫺⫺⫺⫹6410
⫹⫹⫹⫹178
⫹⫹⫺⫺538
⫹⫺⫹⫹088
⫺⫺⫹⫺628
⫹⫹⫺⫹123
⫺⫹⫺⫺112
⫺⫺⫹⫹112
⫺⫽no neglect, ⱖ20th percentile; ⫹⫽neglect, ⬍20th percen-
tile.
752 NEUROLOGY 62 March (1 of 2) 2004
average neglect percentile makes an independent contribu-
tion to the prediction of family burden above and beyond
that predicted by FIM.
Lesion localization analyses. Patients for lesion local-
ization analyses were 126 patients who had CT/MRI evi-
dence of at least one lesioned area. As described in
Methods, 10 neuroanatomic regions were included in the
analyses and coded by two raters. Data on interrater reli-
ability are reported in E-Results: Reliability study at
www.neurology.org.
Lesion patterns: Patients with and without neglect. The
first analysis examined whether neglect and non-neglect pa-
tients exhibited differences in lesion location(s). Categori-
cal modeling using the CATMOD procedure
32
was used to
assess whether neuroanatomic region(s) of involvement
predicted the presence or absence of neglect, and whether
region(s) of involvement predicted neglect subtype. The
proportion of patients in each group with a lesion in each
area of interest can be seen in figures 1 and 2.
See E-Results: Categorical modeling at www.neurology.
org for a description of statistical analyses.
CATMOD was used to establish a distribution of vari-
ance for a 2 ⫻2⫻10 contingency table, for neglect (non-
neglect versus neglect) ⫻chronicity (acute versus chronic) ⫻
lesion area (lesion present or absent in each of 10 areas).
Three main effects and all possible interactions were spec-
ified. With an alpha level of 0.05, main effects of neglect
(
2
[1, n ⫽126] ⫽13.23, p⬍0.001), chronicity (
2
[1, n ⫽
126] ⫽7.52, p⬍0.01), and area (
2
[9, n ⫽126] ⫽120.08,
p⬍0.001) were all significant, as was a three-way inter-
action between neglect, chronicity, and area (
2
[9, n ⫽
126] ⫽25.02, p⬍0.01). No other interactions were signif-
icant. The main effect of area reflects the fact that lesions
did not occur equally in all neuroanatomic regions. The
main effect of neglect indicates that the probability of le-
sioned areas was 1.8 times higher in neglect than in non-
neglect patients. Post hoc testing revealed that 13 of the 37
A⫹patients (45%) had four or more lesioned areas, com-
pared to 7 of the 42 A- patients (17%). Similarly, 22 of the
35 C⫹patients (63%) versus 13 of 43 (30%) C- patients had
four or more lesioned areas. Both comparisons are significant
(
2
⬎9.1, p⬍0.01). The main effect of chronicity indicates
that the probability of lesioned area(s) was 1.6 times higher
in chronic than acute patients. The three-way interaction
indicates that significantly different lesion patterns are asso-
ciated with neglect in acute as compared to chronic patients
(figure E-1, available at www.neurology.org).
Post hoc analyses indicated that in acute patients, le-
sions in the basal ganglia (
2
⫽8.1, p⫽0.004) and in the
inferior/mesial temporal region (
2
⫽4.9, p⫽0.03) were
more likely to be associated with neglect than not, and
there was a slight trend in the same direction for the
superior temporal/middle temporal gyri (p⫽0.11). In the
chronic patients, lesions in the cingulate/orbitofrontal re-
gion (
2
⫽9.6, p⫽0.001), inferior/mesial temporal lobe
(
2
⫽4.1, p⫽0.05), superior/middle temporal lobe (
2
⫽
4.1, p⫽0.05), inferior parietal lobe (IPL) (
2
⫽7.6, p⫽
0.01), and occipital lobe (
2
⫽6.6, p⫽0.02) were more
likely to be associated with neglect than not. In the chronic
group, there were also trends for lesions in sensory-motor
cortex (
2
⫽3.9, p⫽0.07) and superior parietal lobe (
2
⫽
3.4, p⫽0.08) to be more likely associated with neglect
than not. These data suggest that several regions, includ-
Figure 2. Top graph shows proportion of patients having
lesions in defined neuroanatomic regions of interest (ROI)
with perceptual neglect (black bars), as compared to motor
neglect, both perceptual and motor neglect, and neither
perceptual nor motor neglect (white bars). Bottom graph
shows proportion of patients having lesions in defined ROI
with motor neglect (black bars), as compared to perceptual
neglect, both motor and perceptual neglect, and neither
perceptual nor motor neglect (white bars). The asterisk
marks the sole significant difference. Cin/OF/PF/WM ⫽
cingulate, orbitofrontal, prefrontal, periventricular white
matter; SM ⫽sensory-motor; ST/MT/IT/MesT ⫽superior
temporal, middle temporal, inferior temporal, mesial tem-
poral; IP ⫽inferior parietal; SP ⫽superior parietal; BG/
T h/I C ⫽basal ganglia, thalamus, internal capsule.
March (1 of 2) 2004 NEUROLOGY 62 753
ing the inferior/mesial temporal, middle/superior temporal,
inferior parietal, basal ganglia, and occipital lobes, are all
more likely to be involved in neglect than non-neglect
patients.
Lesion patterns: Neglect subtypes. The second CATMOD
analysis examined whether patients with motor neglect, per-
ceptual neglect, both motor and perceptual neglect, or nei-
ther exhibited different lesion patterns (see E-Results:
Lesion patterns of subtypes at www.neurology.org). As
shown in figure 2, patients with perceptual neglect were
more likely to have lesions in the temporal lobe than were
patients in the other groups.
Role of temporal lobe involvement. These data are po-
tentially consistent with recent claims that 1) neglect is
critically dependent upon lesions to the superior temporal
gyrus (STG) and associated subcortical structures,
4
and 2)
previous assertions of the importance of parietal struc-
tures have been confounded by the presence of patients
with visual field defects. See E-Results: Temporal lobe in-
volvement at www.neurology.org for details. There are
three predictions deriving from these claims. Prediction 1
is that there should be an absence of patients with STG
lesions without neglect. Prediction 2 is that there should
be an absence of patients who have neglect without STG
lesions. If previous claims that neglect is linked to IPL and
TPO damage are an artifact of the inclusion in those stud-
ies of patients with field cuts, then prediction 3 is that
there should be an absence of patients with lesions in IPL
and TPO who have neglect without field cuts. For the
analyses addressing these questions, lesions were coded
according to 37 regions of the Damasio and Damasio
25
tem-
plate, plus eight additional subcortical regions in the basal
ganglia, thalamus, and white matter.
The first analysis, relevant to prediction 1, indicated
that there were patients with STG lesions without neglect:
of 50 patients with STG lesions, 16 (32%) did not exhibit
neglect. Six of these 16 were acute and 10 were chronic. None
had visual field deficits. The second analysis, relevant to pre-
diction 2, indicated that there were neglect patients without
STG lesions: of 65 patients with neglect, 37 (57%) had no
involvement of the STG. Twenty of the 37 were acute and
17 were chronic. Twenty-three of the 37 (62%) had no
visual field deficits. Seventeen of the 37 had no basal gan-
glia or thalamic involvement. In this subsample of 17 pa-
tients, the parietal lobe was involved in 13, frontal lobe in
2, and occipital in 2.
In the analysis relevant to prediction 3, we determined
that there were patients with IPL/TPO lesions and no field
cuts who nevertheless exhibited neglect: of 44 patients
with IPL/TPO lesions (P1, P2, T9, O4), 33 did not have
field cuts. Of these 33 patients, 17 (51%) had neglect. Five
of the 17 were acute and 12 were chronic. Thirteen of the
17 had no basal ganglia or thalamic involvement.
Effect of number of lesioned areas on disability, de-
creased attention, and family burden. If number of le-
sioned regions is viewed as a proxy for lesion size, patients
with neglect in our study have larger lesions than those
without the disorder. One obvious question is whether
many of the findings reported here suggesting greater dis-
ability (e.g., lower FIM scores), more cognitive dysfunction
(e.g., longer response times to visual stimuli), and in-
creased burden on families in neglect patients can be re-
duced to an effect of number of lesions (or overall severity
of neurologic dysfunction).
First, we assessed whether there was a relationship
between number of lesioned areas and FIM scores. For
these analyses we used 45 coded regions (37 from the tem-
plates of Damasio and Damasio,
25
and 8 additional subcor-
tical regions). Number of lesioned areas was weakly
negatively correlated with discharge FIM total score (r ⫽
⫺0.3, p⫽0.03), and there was a trend in the same direc-
tion for admission FIM total (r ⫽⫺0.2, p⫽0.08). We next
performed several regression analyses to assess whether
neglect scores predicted patients’functional disability and
family burden when number of lesioned areas was factored
in (see E-Results: Regression analyses at www.neurology.
org). Number of lesioned areas made no statistically reli-
able contribution to the prediction of performance. In con-
trast, neglect scores were strong independent predictors of
both dependent variables.
Discussion. Data from 166 patients with right
hemisphere stroke corroborate previous findings of
the prevalence and impact of neglect in post-acute
populations. In addition, the results indicate that
neglect has an impact upon basic attention, func-
tional disability, and family burden that is signifi-
cantly greater than that predicted by number of
lesioned areas. This suggests that it is the neglect
syndrome per se, rather than overall stroke severity,
that predicts poor outcome in right hemisphere
stroke. Given the strength of the association between
neglect and disability, future studies of neglect treat-
ment efficacy may benefit from including measures
of disability and family burden as indices of treat-
ment success.
The current data also support previous claims that
neglect is a complex constellation of symptoms. We
observed numerous patterns of association and dissoci-
ation of personal, peripersonal, motor, and perceptual
neglect. Pure motor, perceptual, and peripersonal ne-
glect were not infrequently observed. On the other
hand, isolated personal neglect appeared rarely. The
observed dissociations support the proposal that there
are identifiable neglect subtypes. This has potential
implications for investigators undertaking treatment
studies, as the success of a particular treatment may
be linked to patients’subtype profile. The first step in
exploration of such relationships is the inclusion of
subtype data in future studies of treatment efficacy.
Based on the fact that task effects have proven to
be strong determinants of the performance of neglect
patients,
33
one caveat is that different results may
have been obtained had we used other, or additional
measures of the subtypes. The distinction between
motor and perceptual neglect, for example, has been
assessed with pulleys, mirrors, landmark tasks, and
video monitors
5,6,34-36
and these measures tend to dis-
agree in their characterization of patients.
37
Another
limitation, as noted above, is that our measure of
motor neglect confounded intentional neglect and di-
rectional hypokinesia. An additional concern is the
adequacy of the number of tasks employed, as well
as the sensitivity of these tasks. For example, we
754 NEUROLOGY 62 March (1 of 2) 2004
used only a single measure of personal neglect—the
fluff test. Also, the version of the fluff test we
adopted, which permits patients to find targets on
the body with eyes open, may not have been suffi-
ciently sensitive to detect personal neglect. It re-
mains possible that some or all neglect subtypes
occur more frequently than reported here. Another
concern is sampling bias. The study criteria involved
exclusion of patients with attentional or cognitive
deficits so severe as to preclude participation, were
biased by those who were willing to participate (with
willingness itself possibly affected by presence or ab-
sence of neglect, and anosognosia), and were un-
evenly biased by greater relative participation of
Italian than American patients. This may limit the
generalizability of our determination of neglect prev-
alence. We also did not perform studies of test reli-
ability (intrarater, inter-rater, or inter-center), and
although test administration was standardized, it is
nevertheless possible that differences in testing pro-
cedures may have affected results. Finally, as noted,
there was no statistical adjustment for multiple test
comparisons performed. For all of these reasons, cau-
tion should be used in interpreting the study results.
The lesion data are not consistent with the claim
that lesions of the superior temporal lobe are critical
in producing neglect. Nor are they consistent with
the suggestion that previous reports of the impor-
tance of IPL and TPO lesions were confounded by
inclusion of patients with field cuts. On the other
hand, patients with the perceptual subtype of neglect
were twice as likely to have damage to temporal lobe
structures as were patients with motor neglect, per-
ceptual and motor neglect, or neither. Given that
previous investigators did not perform subtype anal-
yses, a possible reason for the disparity is that the
previous sample contained a relatively large number
of pure perceptual neglect patients.
There are several differences in the methods used
previously and the present study. The previous in-
vestigators required evidence of neglect on at least
two clinical tests, whereas we required evidence on
only one test; thus we may have included patients
who were relatively mild. Even with this more inclu-
sive criterion, however, we still found patients who
had STG lesions without neglect. Additionally, the
previous study used a method of lesion overlap,
rather than an examination of individual patients for
the presence or absence of involvement in the critical
regions. Thus, their determination of the most likely
locus of involvement in patients with neglect and
without field cuts might be correct, while still not
speaking to the critical substrates of the disorder.
There are several possible interpretations of the
present data. One interpretation is that we may
have simply failed to detect one or more key regions
damaged in all neglect patients based on the limited
sensitivity of the (predominantly CT-derived) data,
or because the regions are affected indirectly, by di-
aschisis, and thus cannot be visualized on CT or MRI
scans.
38
Alternatively, the data are consistent with
the possibility that neglect may result from lesions to
any one of several regions within a distributed net-
work mediating basic (nonlateralized) and spatial as-
pects of attention.
Acknowledgment
The authors thank Dr. Barbara Browne, Dr. Arthur Gershkoff, Dr.
Anne Marie McLaughlin, Dr. Francesca Meneghello, Sam Pierce,
Megan Reilly, Dr. Kelli Williams, and Dr. Gabriele Zeloni for refer-
ring patients or for assisting with data collection and analysis.
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