Neuropsychotopm, Vol 11, N¢ 2, pp. 115125, 1993 .
Printed in Great Britain .

W29-393'93 96-011+090
[: 1993 Perganion Press Ltd

LEFT AND RIGHT HEMISPHERE CONTRIBUTION TO
RECOVERY FROM NEGLECT AFTER RIGHT HEMISPHERE
DAMAGE-AN [ 18 F]FDG PET STUDY OF TWO CASES
D . PERANI,*t Cr, VALLAR,t E. PAULESU,t M, ALBERONIt and F . FAZIOt
tINB-CNR, University of Milan, Scientific Institute H San Rafaele, Milan . Italy ; and tlstituto di Clinica
Neurologica, University di Milano, Italy
(Received 30 March 1992 ; accepted 14 August 1992)

Abstract--A 2-["F]-Fluoro-2-Deoxy-v-Glucose ([ 1 °F]FDG) and positron emission tomography
(PETI study was performed in the acute and chronic phase of stroke in one patient with unilateral
neglect due to a right hemispheric lesion . In the acute phase, severe neglect, as well as
hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated .
At follow-up evaluation the patient showed an almost complete recovery from unilateral neglect . This
was associated with a return of left hemisphere metabolism to normal values and partial metabolic
recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired .
Another patient with an extensive right cerebral i .schaemic lesion on CT and severe unilateral neglect
was studied by PET in chronic phase . A severe metabolic depression in the left unaffected hemisphere
and in the right cerebral areas spared by the lesion, was found . These data suggest that the remission
of unilateral neglect might he associated to a functional metabolic recovery in both the undamaged
left hemisphere and the unaffected regions of the right hemisphere.

INTRODUCTION
UNILATERAL SPATIAL neglect is typically produced by damage of the right cerebral hemisphere .
The lesions, as assessed by pathological examination or CT scan, most frequently involve the
inferior parietal lobe, but neglect may also occur after frontal or subcortical damage [33] . In
most stroke patients neglect recovers over time, The size of the right-sided lesion is the main
anatomical predictor of improvement : the smaller is the right-sided lesion, the better is recovery
[16, 21] . A few studies using functional imaging methods for measurement of cerebral blood
flow and metabolism have been recently performed in neglect patients with subcortical vascular
lesions [2, 7, 27] . In these reports, the main finding, by means of a semiquantitative right/left
hemispheric assessment, was a functional derangement (reduced blood flow or metabolism) in
the cortex ipsilateral to the lesion, which appeared normal on CT . The follow-up study of
VALLAR et rd . [34] has shown that in patients with vascular right subcortical lesions,
spontaneous recovery from neglect parallels the reduction of hypoperfusion, measured by
SPECT, in the undamaged cortical regions of the right hemisphere . These few available data
from neglect patients suggest, therefore, that a possible neural mechanism of recovery involves
restoration of function in the undamaged regions of the right hemisphere . Studies in the monkey
have shown that also the hemisphere contralateral to the lesion which has produced neglect
*Address for correspondence : Daniela Permit . 1'4B-CNR_ Scientific Institute H S Raflycle, Via Olgcttina 60,
20132 Milano . Italy .
115

116

I) . PERANI et al .

may be involved in the recovery processes [11, 19 ; 36] . However, no quantitative data on
regional cerebral function of the leftft hemisphere in behavioural recovery are available in man .
We measured glucose metabolism by 2-[t"F]-Fluoro-2-Deoxy-D-Glucose ([t"F]FDG) and
positron emission tomography (PET) in two patients with unilateral neglect due to a right
cerebrovascular lesion . One patient was studied longitudinally, in the acute and chronic phase,
the other 4 months after the onset of stroke .

MATERIAL AND METHODS
Neu)opsychological assessment

Visuo-spatial neglect was assessed by the following tasks : (I) circle cancellation [5] ; (2) letter cancellation L13] ; (3)
sentence reading; (4)Wundt Jastrowillusiontest[22] .Inthecancellationtasksthepatientsweterequiredtocross-out
left- and right-sided targets by making use of the right hand . In the reading task the patients had to read aloud 10
newspaper headlines . Normal subjects have an errorless performance in the circle cancellation and reading_ tasks, while
neglect patients typically make let-sidcd omission errors . In the letter cancellation task the maximum difference
between left-and right-sided omission errors is 4 [22] . In the illusion test the patients were required to judge whether
two black fans are or are not equal in length . The illusional effect, whereby one fan appears longer, is produced by
either the left or the right half of the fan . Neglect patients fail to show the normal left-sided illusion effect .
PET method

['8F]FDG PET studies were performed in resting state using a four ring whole-body positron emission lonrograph
(Siemens/CPS, 931-04/I2) . The scanner allows the simultaneous acquisition of data from seven axial planes (four
direct and three cross planes), slice thickness 6 .75 mm, covering an axial field of view (FOV) of 5 .4 cut . The image
spatial resolution for a line source in air, positioned in the centre of the field of view, was 6 .1 Full Width at Half
Maximum (FWHM) [31] . A transmission scan was taken, using ring sources of "Go, to measure attenuation in the
scanned cross-sections for later use in attenuation correction . Patients were positioned on the scanning bed, with the
head symmetrically aligned along the orbitomeatal line . resting in an individually-made rigid polyurethane foam head
mould . Patients were studied with open eyes, in a darkened, quiet room . Acquisition protocol consisted of blank and
transmission scans for attenuation correction, tracer injection, and emission scan in the steady states edition . 250- 300
MBq of ["F] FDG were injected as a bolus, followed by a rapid arterial blood sampling to obtain the arterial input
function . Arterial blood samples were collected every 2 3 sec in the first minute, then at 1.5 .3 .0 .5 .0 .7 .5 . 10, 15, 25, 35 .45
and 65 min from the injection time . Forty-five minutes from the tracer injection (steady state), two spatially consecutive
emission scans (10 min each), needed to covert he whole brain, were acquired by an automatic software control of the
bed position- Fourteen axial slices, parallel to the orbito-nteatal line, were thus obtained . The blood samples were
centrifuged for plasma separation and the radioactivity in the plasma was measured using a sodium iodide well counter .
Images were reconstructed using a filtered hack-projection algorithm with a Hann filter lout-off frequency 0 .5
cycles/'pixel) . The images were zoomed by a factor 3, resulting in an effective pixel size of 1 .57 mm . Values of local
cerebral metabolic rate of glucose (LCM RG Ic) were calculated according In a model based upon the a utoradiographic
technique prospoed by SOKOLOFY e( al. L30] and revised by RaivtcH et al . [29] for human PET studies.
Data analysis
Reconstructed images were analysed on SUN (SPARC) work stations . Image processing was perforated with
Analyze software (BRU,/Mayo Clinic) . Numerical data were obtained using circular regions of interest with a diameter
corresponding to 15 FWHM (9 .6 nun), manually drawn on all cortical and suhcortical structures . Average values of
LCMRGIc were calculated front the multiple ROIs included within the major anatomical subdivisions, which were
identified making reference to an anatomical atlas [12] . These average values, corresponding to the 34 anatomized
regions listed in Table 2 were used for statistical analysis . The same atlas was used to identify on the CT scans the
PEI data analysis since reliable measures of glucose consumption are
damaged areas. These were excluded front the
prevented by methodological problems related to I .CMRGIc modelling in structurally damaged areas, such as in the
case of infarction [311 'he LCMRGIc values ofpatients in acute and follow-up stages were compared with control values in seven normal
subjects (age 51 .28 112 .53) . For each anatomical region, averaged LCMRGIe in neglect patients were considered
pathological when outside 2 S .D . from averaged I .CMRGlc of normal controls . 'I he I-CMRGlc values of Case I were
submitted to an analysis of variance with two within-subject factors : time of assessment (initial and follow-up PET
study) and hemisphere (right and left) . In Case I the pulamen and caudate structures were excluded from the analysis
due to the presence of a right hemisphere hacmatoma The cerebellum was not included due to the presence or

RECOVERY FROM NEGLECT AFTER RIGHT HEMISPHERE DAMAGE

117

contralateral diaschisis, In Case 2, the amount of cerebral metabolic involvement was evaluated according to the
number of regions of interest with LCMRGIc outside 2 S .D . from normal values.

Case reports
Case 1 . A 65-year-old woman, with a long-lasting medical history of hypertension, was
admitted to hospital on 4 March 1990, after the sudden onset of weakness of the left limbs . She
was alert and co-operative . A neurological examination showed a left hemiplegia with
increased deep tendon reflexes, left hemianaesthesia for touch and pain, and left homonymous
hemianopia. The patient had 5 years of schooling, was right-handed on the Oldfield
questionnaire (12/12), [25], and had no family history of left-handedness . A CT scan
performed on the day of admission revealed a hyperdense lesion involving the right basal
ganglia and internal capsule, interpreted as a cerebral haematoma (Fig . 1) . No abnormalities
were detected on doppler sonography . The patient was not aware of her neurological deficits
and showed mild personal neglect . When tested for hemispatial neglect, 2 days later, she
showed extrapersonal neglect in a number of visuo-spatial tasks (Table 1) . The same day she
underwent a [ 15 F]FDG PET study for the evaluation of regional cerebral metabolic rate of
glucose (LCMRGIc) . In this acute stage, an extensive reduction of metabolism in both cerebral
hemispheres, more severe in the right affected side (with values below 2 S .D . the mean normal
average of LCMRGIc) was demonstrated (Table 2 ; Fig . 2A) .
A follow-up examination was performed 8 months later. The patient completely recovered
from hemianaesthesia ; hemianopia was no longer present, but visual extinction to double
simultaneous stimulation was found . The motor deficit improved both in the upper and the
lower limbs . Recovery from visuo-spatial neglect was virtually complete, with a minor residual
deficit in the letter cancellation test (Table 1) . Personal neglect and anosognosia were no longer
present . A control CT scan showed a hypodensc lesion in the right basal ganglia,
corresponding to the outcome of the haematoma . Recovery of the bilateral cerebral metabolic
depression was demonstrated on the second PET study (Table 2 ; Fig . 2B) . LCMRGIc values
below the cut-off score were still present in the right fronto-temporo-parietal areas, while an
almost complete recovery of hypometabolism was demonstrated in the left, unaffected
hemisphere . The analysis of variance showed significant main effects of hemisphere
[F=104 .15, d .f .=1,30, P<0 .0001] and of time of assessment [F=39 .98, d .f.=1,30,
P<0 .0001] . The interaction was also significant [F=21 .13, d .f.= 1, 30, P<0 .0001] . This was
explored by a test of simple main effects . The difference between the two hemispheres was
significant both at the first [F=150 .42, U .- 1, 30 ; P<0 .0001] and the second [F=71 .32,
d .f. = 1, 30, P<0 .0001] PET study . The difference between the two assessments was significant
both in the right [F=6 .41, d .f.=1, 30, P<0 .017] and in the left [F=69 .50, d .f .=1, 30,
P<0 .0001] cerebral hemisphere . In right hemisphere the regions with LCMRGIc values
(ml/100 g/min) below the 2 S .D . cut-off score were 32/32 in the first and 25/32 in the second
PET examination [7 2 =7 .86, d .f.=1, P=0 .005] . In the left hemisphere, the regions with
LCMRGIc values below the cut-off were 26/34 in the first and 7/34 in the second PET study
[7 2 =21 .25 ; d .f=l ; P=0 .001] .
Case 2 . A 67-year-old man, with 17 years of schooling and a medical history of heavy
smoking and untreated hypertension, suddenly developed a left-sided hemiparesis in
September 1990 and was admitted to hospital . The patient was right-handed (12/12) at the
Oldfield questionnaire [2l] . A neurological examination revealed a left homonymous
hemianopia, left supranuclear facial palsy and left hemiplegia . Touch and pain sensation
were abolished on the left side and a steady right-sided deviation of the head and gaze was

Its

I). PERANI et al .

also present . A large hypodense lesion corresponding to a cerebral infarct involving the right
middle and posterior cerebral artery territory was found on CT scan . A ncuropsychological
evaluation revealed a severe extrapersonal visual neglect (Table 1) . A mild anosognosia for
hemiplegia was present .
At a 4-month follow-up examination the neurological deficits were unchanged . A large
right cerebral hemispheric lesion, sparing the anterior cerebral artery territory, was
confirmed on a control CT scan (Fig . 3) . A neuropsychological evaluation showed the
persistence of severe visuo-spatial neglect (Table 1) . The patient was submitted to a
[ 18 F]FDG PET study, which revealed a severe and widespread metabolic reduction in the
left hemisphere and in the right frontal, unaffected regions : the left hemisphere regions with
metabolic values below the cut-off score were 32/34 (Table 2) .
DISCUSSION
Studies using PET and SPELT in patients with cerebrovascular disease have revealed a
reduction of cerebral perfusion or metabolism in undamaged cerebral regions remote from
the structural lesion [3] . The term "diaschisis", originally proposed by voN MoNAKow [24]
on a clinical basis, is currently used to describe these distant effects attributed to neural
deafferentation [15] . A few studies also investigated the relationships of this functional
cerebral involvement with neurological and neuropsychological deficits [9, 23, 26-28] .
The present cases show different metabolic patterns associated with different courses of
spatial neglect . Case 1, who has a comparatively small subcortical lesion, displays a
substantial, albeit not complete, recovery from neglect and neurological deficits . These
behavioural changes were paralleled by an almost complete normalization of the severe
hypometabolism, which, in the acute phase, was present both in the left and right
hemisphere . The second PET study showed, however, a persistent hypometabolism in areas
which belong to networks involved in spatial representation, such as the right fronto-parietal
and thalamic regions [32] . A parallel between behavioural recovery and reduction of
hypometabolism in the hemisphere contralateral to the lesion has not been reported so far .
On the other hand, the observation of a reduction of diaschisis in the unaffected right
occipital and temporal areas in Case I is consistent with previous findings, which have
suggested a role of the undamaged regions of the right hemisphere in the recovery processes
[34] . Thecomplete recovery of glucose metabolism in the right primary visual areas parallels
regression of hemianopia (see comparable data in Ref . [8]) . Case 2, who has an extensive
cortico-subcortical lesion, associated with persistent neurological deficits and severe neglect,
showed a profound metabolic depression, involving not only the right cerebral areas spared
by the lesion [27, 34], but also the whole of the left hemisphere .
The results in our patients suggest, therefore, that restoration of metabolism not only in
the undamaged regions in the right hemisphere, but also in the left hemisphere, may
contribute to recovery from spatial neglect .
Animal experiments provide support for the view that both the contralateral and the
ipsilateral damaged hemisphere are involved in the recovery processes . CROWNE et al . [111
found that lesions of the frontal eye field produce a contralateral visuo-motor deficit, which
recovers over time . A successive callosal section brings about a worsening of the deficit,
suggesting a role of the undamanged hemisphere, via the callosal commissures, in the recovery
process . However, the deficit produced by the callosal section also lessens over time . This
suggests that the integrity of the callosal pathways is not crucial for recovery, which is likely to

RECOVERY FROM NEGLECT AFTER RIGHT HEMISPHERE DAMAGE

Fig. 1 . Case I
. CT images showing a capsulo-lenticular haematoma .
Fig. 2 . Case 1 . (A) [' 8 F]FDG PET (axial slices) in acute phase showing bilateral cerebral
hypometabolism, more severe in the right affected hemisphere . (B) ['tF]FDG PET in chronic phase
showing the complete metabolic recovery in the left hemisphere and in the posterior cortical areas of
the right hemisphere, where residual hypometaholism is present in the frontal and parietal regions .

119

1 20

D . PrRANI C! a) .

Fig . 3 . Case 2. CT images showing a large ischaemic lesion involving the right middle cerebral artery
territory and the right occipital lobe .

RECOVERY FROM NEGLECT AFTER RIGHT HEMISPHERE DAMAGE

Table 1 . Casc 1 . (A) Performance in tasks assessing visuo-spatial neglect
in the first (I) and follow-up (II) assessments . The scores are left-sided
errors . The patient did not make right-sided errors . (B) Contralateral
(left) neurological deficits on a standard neurological examination [4] .
Score : 0 (normal), 1/2/3 (mild, moderate, severe deficit) . In the case of
somatosensory and visual half-field deficits score I indicates contralateral extinction to double simultaneous stimulation . (C) Anosognosia
for motor and visual half-field deficits ; score 0-3 (absent-to-severe) [6] ;
n .e
. : not examined due to recovery from the neurological deficit
1

II

3/6
31/53
3/10
6/20

0/6
7/53
0,10
0/20

3
3

2
2

3
3

0
0

2
3

1
1

3
3

0
0

3
3

n .e .
n .e.

Case 1 . Test
(A) Visuo-spatial neglect
Circle cancellation
Letter cancellation
Sentence reading
Wundt-Jastrow illusion test
(B) Neurological deficit
Motor
Upper limb
Lower limb
Somatosensory
Upper limb
Lower limb
Visual half field
Upper quadrant
Lower quadrant
(C) Anosognosia
Motor deficit
Upper limb
Lower limb
Somatosensory deficit
Upper limb
Lower limb
Case 2 . Test
(A) Visuo-spatial neglect
Circle cancellation
Letter cancellation*
Sentence reading
Wundt-Jastrow illusion test
(B) Neurological deficit
Motor
Upper limb
Lower limb
Somatosensory
Upper limb
Lower limb
Visual half field
Upper quadrant
Lower quadrant
(C) Anosognosia
Motor deficit
Upper limb
Lower limb
Somatosensory deficit
Upper limb
Lower limb

I

11

6/6
91/104
3/10
20/20

64/104
IQ/10
20/20

3
3

3

3
3
3
3

3
3

I
1

0
0

1
1

0
0

*In this task the patient failed to cross out letters in the left half of the
sheet and in the left portion of the right half of the sheet .

121

122

D . PEtANI et al .

. The
Table 2 . Local cerebral metabolic rate of glucose consumption (LCMROlc) is expressed in ml/100g/min
cerebral regions are labelled according to the atlas of DAs1ASIO and DAHASto [12], with the corresponding
Brodnmnn's areas in brackets
Normal controls
Regions

LH

RH

1-11
F2
F3
F4
h5
F6
F?
F8
Fit
F12
P1
P2
P3
P4
T3
T4
75
T6
T7
T8
T9
Tl0
TII
T12
Ol
02
03
04
05
01/2
CAU
PUT
THAI .
CBL

6 .06 10 .80)
7 .22 (0 .94)
6 .43 (0 .71)
6 .21 (0 .66)
6 .57 (0 .91)
637 (0 .70)
6 .63 (0 .60)
6 .57 (0 .66)
5 .93 (0 .62)
5 .96(046)
6 .14 (0 .44)
6 .48 (0 .58)
6 .84 (0.89)
7 .61 (1101
5 .70 (0 55)
6 .37 (0.631
5 .10 (0.62)
5 .90 (0.50)
6 .53 (0.42)
5 .34 (0.46)
6 .24 (0.57)
4 .49 (0 .40)
5 .23 10.66)
4 .34 (0.571
7 .08 (( .41)
7 .35 (0.92)
5 .90 (0.691
6 .42 (1 .02)
6 .42 (0 .971
7 .84 (1 .32)
6 .37 (0 .59)
6 .70 (0 .71)
6 .32 (0731
S .56 (0 .68)

5 .98 (0 .63)
7 .31 (1 .03)
6 .28 (0 .60)
6 .10 (0 .98)
6 .54 11 .02)
6 .51 (0 .64)
6 .56 (0 .711
6 .59 (0 .67)
5 .89 (0 .67)
5 .88(0 .451
6 .33 (0 .61)
6 .59 (0 .65)
6 .92 (0 .62)
7,54 (0 .94)
569 (0156)
6 .19 (0 .60)
5-06 (0 .58)
5 78 (0 .52)
6 .47 (0 .71)
5 .45 (0 .49)
6 .32 (0 .53)
4 .32 (043)
5 .31 (058)
4 .25 (0 .23)
6 .90 (033)
7 .31 (0 .89)
5.80 (0 .69)
6 .48 (0 .80)
6 .55 (1,13)
7 .62 (1 .28)
6 .38 (0 .56)
6 .70 (0 .65)
6 .44 (0 .77)
5 .56 (0 .62)

Case I

Case 2

Ist study
LH
RH

2nd study
LH
RH

PET study
LH
fill

4.67*
5 .08*
5 .27
437*
4 .86
4 .44*
4.33*
4 .66'
3 .88*
4 .30*
4 .38*
4 .81*
4 .18*
5 .15*
4 .10*
4 .10*
4 .25
4 .38*
5 .52*
4 .51
4 .99*
3 .07*
3 .80*
3 .48
413*
5.19*
4 .04*
4 .16*
4 .70
5 .35
4 .95*
6 .36
4,59*
3 .35*

4.74*
4 .36*
5 .65
5 .00
5 .07
5 .31
5 .27*
5 .77
4 .09*
4 .47*
5 .45
6 .04
5 .37
5 .93
4 .95
5 .20
4 .66
5 .68
6 .39
4 .80
6 .11
3 .70
5 .54
4 .03
5 .44*
6 .88
4 .88
5 .79
6 .30
7 .29
5,10
6.59
5 .45
3 .62*

3 .18*
4 .44*
3 .71*
3 .55*
4 .27*
4 .03*
4.14*
4 .43*
3 .73*
3 .63*
3 .98*
4 .29*
479'
4 .64*
3 .66*
3 .88*
3 .43*
4 .16*
4 .99
3 .98*
4 .36*
2_98*
3 .83*
3 .05*
4 .26*
5 .13*
3 .95*
404*
4 .63
5 .74
3 .85*
4 .84'
4 .86
2 .90*

3 .82*
4 .32*
4 .13*
343*
4.18*
3 .66*
3 .43*
3 .52*
3 .02*
3 .32*
3 .42*
3,74*
3 .85'
4.45'
3 .14*
3 .16*
3 .36*
3 .59*
4 .35*
3 .60*
3 .95*
2 .68*
3 .40*
2 .86'
4 .34*
4 .40'
4 .03*
3 .98'
4 .19#
4 .82*
#
#
3 .20'
4 .73*

3 .97*
4 .26*
4 .14*
3 .46*
4 .85
2 .70*
2 .82*
295*
2 .96*
3 .31*
3 .06*
3 .63*
4 .02*
5 .28*
3 .413 .60*
3 .90*
458*
4 .05*
3 .81*
4 .32*
3 .47'
3 .81*
3 .24*
5 .28'
5 .95
5 .03
5 .17
5 .16
6 .22
#
4
2 .t2*
5 .30

2 .80*
2 .793 .092 .763 .50*
#
246*
#
2 .85*
2 .71*
#
#
#
3 .45*
#
#
9
#
#
#
#
#
#
#
#
#
9
#
#
#
#
#
#
4 .69

Fl : anterior cingulatc gyrus [24] ; F2 : posterior cingulate gyrus [23, 31] ; F3 : mesial supplementary motor area
[6] ; F4 : pre-frontal regions [8 10] ; F5 : mesial rolandic regions [1-4] ; F6 : frontal opereulmn [44 . 45] : F7 : prefrontal regions [8, 9, 46] ; F8 : lateral pre-motor [6] and rolandic [I 4] regions ; Flt : anterior orbital frontal region
1101 ; F 12 : posterior orbital frontal regions [I I-13, 47] ; Pl : supramarginal gyrus [40] ; P2 : angular gyms [39] ; P3,
P4 : lateral and mesial superior parictal lobule L5, 7] ; T3 : anterior part of middle temporal gyrus [21] ; 14: posterior
part of middle temporal gyrus [37] ; T5 : anterior part of inferior temporal gyms [20] ;T6 : posterior part of inferior
temporal gyrus [37] : T7 : auditory region [41, 42] ; T8, T9 : superior temporal gyrus anterior and posterior to
auditory region [22] : 1 MT] I : mesial temporal regions [28 . 36] ; TI2 : polar temporal area [38] ; 01/2 : calcarine
cortex [17] ;01,()2 : infra and supra calcarinc mesial occipital areas [I8, t9] ; 03 : temporo-occipital junction
[37, 36] : 04, 05 : inferior and superior lateral occipital regions [18, 19] ; CAU : caudate nucleus ; PUT. putamen :
THAT : thalamus ; CBL : cerebellum : # : structural lesion .
be mediated by the undamaged regions of the lesioned hemisphere . In line with these findings,
in monkeys with a partially recovered contralateral visual deficit produced by a lesion in the
frontal eye fields, a second lesion in the contralateral frontal eye fields yields a worsening of the
visual disorder [19] .
The present observation of a reduced metabolism in the hemisphere contralateral to the

RECOVERY FROM NEGLECT AFTER RIGHT t1El9SPHERE DAMAGE

1 23

lesion is consistent with findings in patients with unilateral vascular lesions examined by PET
in an early phase after stroke [1, 14, 17, 18, 20] . In the absence of other variables such as
multiple bilateral lesions, large vessel occlusion, transtentorial herniation or drug effects, the
contralateral functional depression associated with a unilateral lesion has been explained in
terms of transhemispheric neuronal diaschisis [14, 18, 20] . This interpretation is supported by
the observation that in baboons the anterior section of the corpus callosum produces a
bilateral depression of cortical metabolism, mainly in the anterior regions [37] . The extent of
transhcmispheric diaschisis may in turn be related to the size of the contralateral lesion : larger
lesions are more likely to disrupt interhemispheric callosal connection, therefore producing a
more severe metabolic depression . In line with this view, Case 2, who had an extensive right
cortico-subcortical lesion, showed a major hypometabolism in the left hemisphere, which did
not recover over time . By contrast, in Case 1 . who had a right subcortical haematoma, the
cortex was undamaged on CT scan, but a severe reduction of metabolism was shown by PET .
This right cortical metabolic depression may in turn have produced, through callosal
connections, a comparatively minor left hemispheric diaschisis, which recovered over time .
Also the site of the cerebral damage may be relevant : small lesions, if strategically located to
disrupt the interhemispheric connections, may bring about a severe eontralatcral hypometabolism (see the experimental callosal sections of YAMAGIJCt-u et al .) [37] .
The present study has shown a correlation between clinical and functional parameters :
recovery from hemineglect and neurological deficits parallels the reduction of hypometabolism
in both cerebral hemispheres . In the follow-up study, Case I showed neurological recovery and
has a mild residual visuo-spatial neglect . The latter may be related to the persistent
hypometabolism in the fronto-parietal and thalamic regions of the right hemisphere, which are
known to be involved in visuo-spatial functions [27, 33] . These findings suggest that the
regression of functional impairment in the left hemisphere contributes to the amelioration of
neglect . However, a complete behavioural recovery requires a total regression of diaschisis in
the undamaged regions of the right hemisphere . Accordingly, in Case 2 the severe diaschisis in
the left cerebral areas, contralateral to a large right-sided lesion, may have prevented the
takeover of neuropsychological functions by the left hemisphere .
The present suggestion of a bi-hemispheric contribution to recovery from neglect and
neurological deficits is in line with recent PET findings in patients with hemispheric vascular
lesions, who recovered from hemiplegia . Finger movements of the contralateral recovered
hand activate a number of bilateral regions (sensorimotor, premotor, and inferior parietal
cortex, cerebellum . etc .) . By contrast, movements of the unaffected fingers activate mainly the
contralateral hemisphere [10] (see also Ref . [35]) . This suggests that recovery of motor
function is mediated by a bilateral neural network .
Finally, the relative contribution of the two hemispheres may not be fixed, but vary over time .
For instance, the role of the undamaged left hemisphere may be more important in an early
phase after stroke, when the right hemisphere dysfunction is maximal . In a later recovery stage
the role of the undamaged regions of the right hemispheremay become more and more relevant .
Acknowledgement-Supported in part by CNR and

MURST grants.

REFERENCES
I . ANDREws, R, J . Transhemispheric diaschisis : A review and comment . Stroke 22, 943-949, 1991 .
2 . BARON, J. C . . D'ANTONA . R ., PANTANO . P_. SERD.ARU. M ., SAMSON, Y . and HousstR, M . G . Effects of thalamic
stroke on energy metabolism of the cerebral cortex . Brain 109, 1243-1259, 1986 .

1 24

D . PeRAw ei al .

3. BARON, J . C ., FRACKOWIAR, R . S. J ., HERHOLZ, K ., Joyrs, T. . LAMS5ERTSMA, A .A ., M.AZOYER, B . and
WwNHARO, K . Use of PET methods for measurement of cerebral energy metabolism and hemodynainics in
cerebrovascu]ar disease . J . cereb . Blood Flow Metab. 9, 723-742, 1989 .
4. BISIAGH, F ., CAPRA, S . F . and VALLAR . G . Guida alfEsame Neuropsicologico . Cortina, Milano, 1983 .
5 . BISIACII, E . . LUZZATTI . C . and PERANI, D . Unilateral neglect, representational schema and consciousness . Brain
102,609-618,1979 .
6 . BISIACH .E .,VALLAR,G .,PERANI .D .,P.APAGNO,C.andBERILA .Unawarenessofdiseasefollowinglesionsofthe
right hemisphere : anosognosia for hemiplegia and anosognosia for hemianopia . .Neuropsyehologia 24,471 482,
1986 .
7 . BocuusSLAVSi.Y, J„ MIKLOSSY, J„ REULI, F ., DERLAZ, J.-P ., ASSAL . G . and DFIA10YE, B . Subcorteal neglect :
Neuropsychological, SPECT . and neuropathologieal correlations with anterior choroidal artery territory
infarction . Ann . Neural . 23, 448352, 1988 .
8 . BOSLEY, T . M . . DANN . R_. SILVER, F . L . . ALAVI, A ., Kt15HNER . M ., CHAWLCK, J . H . SAVING, P . J ., SERGOTT,
R . C ., SCHAV, N .J . and RElvIUH, M . Recovery of vision after ischemic lesions : Positron Emission
Tomography . Ann . Neurol. 21, 444-450, 1987 .
9 . BOSLEY, T . M ., ROSENI2uisT, A . C-, KI .SHNER, M ., BURKE, A ., STEW . A ., DANN, R . . COBBS, W . . SAVING, P . L
SCHATZ, N . J ., ALAVI, A . and Raivicn, M . Ischemic lesions of the occipital cortex and optic radiations : Positron
Emission Tomography . Neurology 35, 470-484, 1985 .
10 . CHOLLET. F . . DI PIERO, V ., Wise, R . J . S ., BROOKS, D . .L, Do] AN . R . J . and FRACKOWIAK, R . S . J . The functional
anatomy of motor recovery after stroke in humans : A study with Positron Emission Tomography . Ann . .Veurol .
29,63-71 .1991 .
11 . CROwan, D . P ., YEO, C . H . and STEELS RUSsrL, I .l'hecffects of unilateral frontal eye field lesions in the monkey :
Visual-motor guidance and avoidance behaviour . Behau . Brain Res . 2, 165-187, 1981 .
12 . DAM.ASIO. 11 . and DAMASIO, A . Lesion Analpsi.s in Neuropsychology . Oxford University Press, New York, 1989 .
13 . DILLER, L . and WEINRERG, J, Hemi-inattention in rehabilitation . The evolution of a rational remediation
program . In Advances in Nemroloyy Vol .. 18, Hemi-inattention and hemisphere specialization, E . A . WEINsruN
and R . P . FRIEULANU (Editors), pp . 63-82 . Raven Press, New York, 1977,
14 . DOBKIN, J . A . . LEVINL, R . L ., LAOREZE, H . L ., DL l .l I, A . D . NICKITS, R . 1 . and RowE, B R . Evidence for
traushemispheric diaschisis in unilateral stroke . Arch . ,Veurol . 46, 1331 1336, 1989 .
15 . FuiNEY, D . M . and BARDS, .1 .-C . Diaschisis . .Stroke 17, 8t7-830, 1986 .
16 . HIER., D . B ., MONDLOCK, J. and CAPLAN, L . R . Recovery of behavioral abnormalities after right hemisphere
stroke, .,Veurology 33, 345-350, 1983 .
17 . KUHL, D. E ., PI WLrs, M. E . . KOWELL, A . P ., METTER, E. i, Saw, C . and WINTER, J . Effects of stroke on local
cerebral metabolism and perfusion : Mapping by emission computed tomography of 18F E'DO and 13NH3Ann . Neurol .8,47 60 . 1980 .
18 . LAGRIZr,H .L .,L¢NINE,R .L.,PIOUI .A,K .I . .,NICKLLs,R .J .,SUNDERLAND, J .S .andBOWL, B .R .Contralateral
flow reduction in unilateral stroke : Evidence for transhemispheric diaschisis . Stroke 18, 882-886, 1987 .
19 . LATTO, R . and CowrY, A . Visual field defects after frontal-eye fields lesions in monkeys . Brain Rev . 30, 1-24,
1971 .
20 . LEN%I, U . L ., PRA(KOWIAK, R . S . .1 . and JONES . 'I' . Cerebral oxygen metabolism and blood flow in human
cerebral ischemic infarction . J. Cereh . Blood Flora MMeln6 . 2.321 -335, 1982 .
21 . LEVwe, 1) . N ., WARAOH, .1 I)., Br\OwITz . 1,. and CAI .vANIo, R . Deft spatial neglectt cOccts nflesion sin: and
plemorbid brain atrophy on severity and recovery following right cerebral infarction . Neurology 36, 362 366.
1986 .
22 . MASSIRONI, M ., ANTONUCCI, G ., PIZZAMIOLIo, L ., VFFALE, M . V and ZOCCOLOrri, P . The Wundt Jastrow
illusion in the study of spatial hemi-inattention . Neuropspchologia 26, 161-166, 1988 .
23 . MATER, J . F . Neuroanatomy and physiology of aphasia : evidence from positron emission tomography,
Aphasiology 1, 3 33 . 1987 .
24 . MoNAKOw, C . vos Die Lokalizalion im Cirosshirn and der Abhau der Funktion durch kortikale Herde .
Wiesbaden: Berniann, 1914 .
25 . OLDEIELo, R. C . The assessment and analysis of handedness . Neuropsyrhologia 9, 97 113 . 1971 .
26 . OLSEN .'1'. S ., BRCHN, P . and OeERS, R . G . P. . Cortical hypoperfuston as a possible cause of subcortical aphasia .
Brain 109,393 410 . 1986 .
27 . PERANI, D ., VALLAR, G ., CAPPA, S . F. . MLssA, C . and FAZIO, F . Aphasia and neglect after subcortical stroke
. A
clinical%cerchral perfusion correlation study . Brain 110, 1211 1229, 1987 .
28 . PERANI,D.,DIPIERO .V .,LECIGNANI,G .,GILARDEM .C .,PANTANO .P.,ROSSETTI,C .,POZZULI,C .,CiERUNDINI,
P . . FAZIo, F . and LENzi, G . I .. Remote effects of subcortical cerebrovascular lesions : a SPECT cerebral
perfusion study . J . nvreb . Blood Flow Metab .8, 560567, t988 .
29 . RuvIt IT, M ., ALAVI, A ., WOW- , A ., FOWLER . J ., ARNETT, C . . MACGREGGR, R . R ., Stout, C . Y ., A I KrNS, H .,
ANAND, A ., DANN, R . and GREENREKQ, J . H . Glucose metabolic rate kinetic model parameter determination in
human, : The lumped constants and rate constants for I SF-fluorodeoxyglucose and I I C-dcoxygluco .se . J . cereh .
Blood Flow Merah . 5, 179-192, 1985.

RECOVERY FROM NEGLECT AFTER RIGHT HEMISPHERE DAMAGE

l25

30 . SOKOLOFP, L., REIvICH, M ., KENNEDY, C ., DES ROSTERS, M . H ., PkILAK, C . S . . PErticRE . K . D., SAKLRAUA, 0 .
and SIIINOARA . M . The 14 C-deoxyglucose method for the measurement of local cerebral glucose utilization :
theory, procedure and normal values in the conscious and anesthetized albino rat . J. Neurochem . 28, 897-916,
1977.
31 . SPINKS, T. J ., JONES, T ., GILARDI, M . C . and HEATFIER, J. D . Physical performance of the latest generation of
commercial positron scanner . IEEE Trans . Nuel . Sci . 35, 721-725, 1988 .
32 . VALLAR, G. The anatomical basis of spatial hemineglect in humans . In Unilateral Neglect : Clinical and
Experimental Studies, 1. H . ROBERTSON and L C . MARSHALL (Editors) . Lawrence Erlbaum, London, in press .
33 . VALLAR, C . and PERANI, D . The anatomy of unilateral neglect after right hemisphere stroke lesions . A clinical
CT/Scan correlation study in man . N'europsychologia 24, 609-622, 1986 .
34 . VALLAK, G. PERANI, D., CAPPA, S . F . . MESSA, C ., LENZ], G. L . and FAZIO, F . Recovery from aphasia and neglect
after subcurtical stroke : Neuropsychological and cerebral perfusion study . J. .Veurol . Neuro.surg. Psychiat . 51,
1269-1276 . 1988 .
35 . WEILLER, C ., CHOLLET, F., FRISTON, K . J ., WISE, R . J . S . and FRACKOwlACK . R . S . J . Functional reorganization
of the brain in recovery from striato-capsular infarction in man . Arm . Nevrol . 31, 463-472, 1992 .
36 . WATSON, R . T ., VALFNSTEIN, E ., DAY, A . L . and HEILMAN, K . M . The effect of corpus callosum lesions on
unilateral neglect in monkeys . Neurology 34, 812 815, 1984 .
37 . YAMACUCHI, T ., KUNIMOTO, M ., PAPPATA, S ., CHAVOIX, C ., RICHE, D., CHEVALIER, L ., MAZOVRR, B ., MAZIERE,
M ., NAQUET, R . and BARON . J . C. Effects of anterior corpus callosum section on cortical glucose utilization in
baboons . Brain 113,937 951, 1990 .