Cortical Reorganization in Patients with
Facial Palsv
Michel Rijntjes,* Martin Tegenthoff, MD,? Joachim Liepert, MD,? Georg Leonhardt, MD,$
Sylvia Kotterba, MD,? Stephan Muller, MD,$ Stephan Kiebel,* Jean-Pierre Malin, MD,?
Hans-Christoph Diener, MD,+ and Cornelius Weiller, MD*
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Possible changes in the organization of the cortex in patients with facial palsy, serving as a model of peripheral motor
deefferentation, were investigated by using transcranial magnetic stimulation (TMS) and positron emission tomography
(PET). With TMS, the size of the area producing muscle-evoked potentials (MEPs) of the abductor pollicis brevis
muscle, the sum of MEP amplitudes within this area, and the volume over the mapping area were compared between
both hemispheres in 8 patients. With PET, increases in regional cerebral blood flow, measured with the standard H,’50,
bolus injection technique, were compared between 6 patients and 6 healthy volunteers during sequential finger opposition. Patients moved the hand ipsilateral to the facial palsy, the control subjects the right hand. Of 9 patients in total,
5 participated in both experiments. With both methods, an enlargement of the hand field contralateral to the facial palsy
was found, extending in a lateral direction, into the site of the presumed face area. The PET data showed that the
enlargement of the hand field in the somatosensory cortex (SMC) is part of a widespread cortical reorganization, including the ipsilateral SMC and bilateral secondary motor and sensory areas. We report for the first time, using two
different noninvasive methods, that peripheral, mere motor deefferentation is a sufficient stimulus for reorganizational
changes in the healthy adult human cortex.
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Rijntjes M, Tegenthoff M, Liepert J, Leonhardt G, Kotterba S, Miiller S, Kiebel S, Malin J-P, Diener H-C,
Weiller C. Cortical reorganization in patients with facial palsy. Ann Neurol 1997;41:621-630
The ability of the cortex to adapt to changing circumstances is called “cortical plasticity” or “cortical reorganization.” Recent studies on animals and humans have
shown changes in cortical organization that are more
extensive and rapid than previously thought based on
static representations, as was suggested by the homunculus of Penfield and Jaspers [I]. Under normal conditions, noninvasive techniques like transcranial magnetic
stimulation
(TMS),
positron
emission
tomography (PET), and functional magnetic resonance
imaging (fMRI) seem to confirm the idea of stable cortical representations. In healthy humans, motor cortex
areas of face, arm, and leg can be clearly distinguished
by focal stimuli with TMS [2]. In PET studies in
healthy volunteers, the hand area is consistently found
between 44 and 64 mm above the intercommissural
line (AC-PC line) [3].
However, Penfield’s findings have been challenged
by the recent interpretation that the motor cortex acts
as a complex network. Studies on the primary sensorimotor cortex (SMC), where a considerable overlap in
finger representation has been found [4, 51, have been
most revealing, since body representations in this re-
gion were believed to be especially stable because of
fixed anatomical connections [6, 71.Experiments to induce changes in cortical organization are essentially
based on rwo principles. The first is to challenge the
cortex to adapt to a different environment. Learning
[8] and training [9] increases, immobilization [lo] decreases, the size of the hand field. Although the change
of size in these experiments was larger than thought
possible, somatotopic boundaries remained intact.
The other principle of reorganization is found after
peripheral or central nervous system lesions. Inside the
hand area of monkeys, reorganization of representations has been shown after finger amputation [I 11 and
artificial syndactyly [ 121. In humans, some studies have
shown even more profound reorganization of the adult
cortex, with representations crossing somatotopic
boundaries. The clinical observation that some patients
with arm amputation experience sensation of the missing hand after cutaneous stimulation of the face [13]
was visualized by studies using PET, TMS [14], and
magnetic encephalography [ 151. Face representation in
such patients had come to include the fallow hand
area, results that correspond to those obtained after up-
From the Departments of Neurology at “University of Jena, tUniversiry of Bochum, and tUniversiry of Essen, and §Department of
Nuclear Medicine, University of Essen, Germany.
Address correspondence to Dr Rijntjes, Neurologische Klinik und
Poliklinik der FSU Jena, Philosophenweg 3, 07740 Jena, Germany.
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Received Feb 22, 1996, and in revised form JuI 22 and Oct 7.
Accepted for publication Oct 7, 1996.
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Copyright 0 1997 by the American Neurological Association
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per limb amputation in primates [IG]. In these studies,
cortical reorganization took place after combined sensory and motor deprivation. In rats, it has been demonstrated, after peripheral motor nerve lesion, that
deefferentation alone can induce similar changes. O n e
week to 4 months after facial nerve transection in adult
rats, the forelimb area occupied t h e former vibrissae
area on the motor cortex [17, 181.
Complex reorganization occurs in patients recovered
from stroke (for review, see Reference 19). In two of
these studies [20, 211, a large lateral extension of the
area activated during finger opposition was found in
some patients, reaching well into the area supposedly
representing the face. This lateral extension has been
found as well in patients with amyotrophic lateral sclerosis when moving the paretic h a n d [22]. To further
substantiate the finding of a lateral extension of the
hand representation in the h u m a n brain, we designed
the present study in patients with peripheral facial
palsy. It was hypothesized that the motor representation of the hand would enlarge into the deefferented
face representation, as indicated by changes of regional
cerebral blood flow (rCBF) during finger movement,
o r determined as the area from which motor response
could be elicited with TMS.
turbance of trigeminal function was found on clinical examination, confirmed by a normal contralateral orbicularis oculi
reflex in each parient. In all patients, the facial palsy developed acutely; in the patients with parotic tumor or acoustic
neurinoma, no facial weakness was apparent before surgery,
but the facial nerve could not be spared intraoperatively. The
patients did not suffer from other diseases of the nervous
system. No patient received central acting drugs during the
investigations. An MRI scan showed an intact brain in each
patient.
Transcranial Magnetic Stimulation
TMS was performed with a Magstim 200 H P device (Magstim, Dyfed, UK) and a figure-eight coil (outside diameter,
8.7 cm; peak magnetic field strength, 2.2 T; peak electric
field strength, 660 V/m), which stimulates predominately
neural structures under its center. Motor-evoked potentials
(MEPs) were recorded with surface electrodes from the contralateral abductor pollicis brevis muscle (APB) on both sides
and stored on an electromyographic (EMG) machine (Neuropack 8, Nihon Kohden, Japan). The band pass was 20 Hz
to 3 kHz, the gain 0.1 to 1 mVID. The magnetic stimuli
were delivered while the patients were seated comfortably in
a chair. During the whole examination, muscle relaxation
was monitored with surface electrodes by EMG (gain, 0.1
mV/D). The lowest intensity producing a motor response in
at least three of six trials (gain, 0.1 mV/D) was defined as
threshold. Threshold was determined over that scalp position
where TMS previously elicited the highest amplitude. Stimulus intensity was 1.2 times the intensity of the motor
threshold. Up to five stimuli were applied to each position.
The largest peak-to-peak amplitude was considered for statistical analysis. Amplitudes smaller than 10 IJ.V were considered as zero value. In each patient, both hemispheres were
examined in random order. Starting at the vertex, the motor
cortex was examined in rostral, dorsal, and lateral directions
in steps of 1 cm until no fiirther MEP could be elicited.
During the whole mapping procedure the coil was held
steadily with the grip pointing backwards. The positions
were identified with the help of a tight-fitting cap with a
coordinate system that was positioned with the Cz-mark over
the vertex using nasion, inion, and the preauricular areas as
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Patients and Methods
Patients
We studied 9 right-handed patients (5 males and 4 females;
age, 25-73 years; mean age, 47 years) with a peripheral facial
nerve palsy (Table 1). In 8 patients, TMS mapping studies
were performed. Six patients were investigated by using PET.
Five patients participated in the TMS mapping as well as in
the PET studies. For comparison, an additional 6 healthy
right-handed male subjects (age, 24-5 1 years) were studied
as controls for the PET study, another 6 healthy righthanded male subjects (19-34 years) for the TMS study. Severity of facial palsy was graded according to the scoring system of House and Brackmann [23]. Duration and
pathogenesis of the facial palsy are listed in Table 1 . N o dis-
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Table 1. Clinical Data of the Patients with Facial Palsy
Patient
Age (yr)
Sex
Side of Palsy
Duration
Cause"
40
41
F
M
F
M
F
Left
Left
Right
Left
Right
Left
Right
Right
Left
3 yr
19 mo
12 yr
3 mo
4 mo
12 yr
36 yr
29 days
7 days
Acoustic neurinoma
Acoustic neurinoma
Cholesteatoma
Parotid tumor
Acoustic neurinoma
Herpes zoster
Perinatal
Idiopathic
Idiopathic
55
67
39
73
36
44
25
M
M
F
M
Gradeb
TMS
PET
X
X
X
X
X
X
X
X
X
X
X
X
X
X
"In the patients with facial palsy due to acoustic neurinoma or parotid tumor, no facial palsy was apparent before the operation.
'The extent of the facial palsy was graded after House and Brackmann [23], in which 0 = no palsy; 1 = mild palsy, no facial asymmetry at
rest; 2 = moderate palsy, eye closure possible, obvious facial asymmetry at rest; 3 = severe palsy, incomplete eye closure, barely visible
movement or tonus; 4 = total paralysis, no movement or ronus.
.+
1MS = transcranial tnagneric srimularion; PET = positron emission tomography.
622 Annals of Neurology
Vol 41
No 5
May 1997
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landmarks. The number of positions from which MEP could
be elicited was calculated and expressed as an area where
each position equals 1 cm2. In addition, the ratio (area of the
hemisphere contralateral to the facial palsy divided by the
area over the ipsilateral hemisphere), the centers of gravity
(COGS),and the sum of MEP amplitudes (FV) were calculated for each hemisphere separately. The volume over the
mapping area (cm2 * FV) was determined using an inverse
distance interpolation and an integration formula. For comparison, the cortical representation areas of the APB muscle
were mapped over both hemispheres in 6 healthy righthanded male subjects (19-34 years); the ratio (area of the left
hemisphere divided by the area of the right hemisphere) was
calculated. For statistical analysis, the Wilcoxon signed rank
test, the Mann-Whitney U test, and Spearman’s rank correlation were used. The level of significance used for all tests
was set at p < 0.05.
Positron Emission Tomography
rCBF was measured with an ECAT 953/15 PET scanner
(CTI Inc, Knoxville, TN) after a slow bolus injection of
maximal 700 MBq H2I5Oper application. After attenuation
correction (using a transmission scan) the data were reconstructed into 15 transaxial planes by filtered back projection
with a Hanning filter with cutoff frequency of 0.5 cycles/
pixel (1.96 mm pixel size), resulting in a full width half maximum (FWHM) resolution of 8 mm in the reconstructed
image. The integrated counts accumulated were used as an
index of rCBF [24]. Each subject underwent 12 consecutive
measurements of rCBF. Six scans were performed at rest and
six scans during the performance of finger movements of the
hand ipsilateral to the facial palsy in the patients and with
the right hand in the control subjects. The movements consisted of sequential opposition of the individual fingers to the
thumb at a frequency of three oppositions every 2 seconds,
paced by a metronome. Prior to scanning, all subjects practiced the task until movements were smooth and effortless.
The rest scans and activation scans were performed alternately. T o compensate for auditory input, the metronome
Table 2. Results of Transcranial Magnetic Stimulation
Quotient
(CH/IH)
Patient
CH
IH
1
2
3
4
26
27
24
35
20
15
31
25
25.4 2 6.2
15
1.73
23
23
14
14
12
23
20
18.0 t 4.7
1.17
1.04
8
Average
of all
patients
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Sum of
Amplitudes
(w v )
Area (cm’)
5
6
7
was also on during the rest scans. This task leads to a robust
increase in rCBF in normal subjects [25]. Due to the small
axial field of view of the camera (5.4 cm), the gentry was
oriented to include the upper part of the brain including the
supposed hand area in its upper part. In effect, data were
available for all subjects from 16 to 52 mm in the standard
space. The scans of each individual were realigned to each
other to correct for interscan movement artifacts. A threedimensional (3D) MRI of the brain was obtained for all subjects. An averaged image of the 12 PET runs was reoriented
to the individual 3D MRI scan using statistical parametric
mapping (MRC Cyclotron Unit, Hammersmith Hospital,
London, UK). The parameters thus obtained were used to
transform all 12 PET scans to the MRI space. PET and MRI
data of those patients with left-sided palsy were flipped in
the sagittal plane to enable comparison with the control subjects. The 3D MRI scans of each individual, after being
stripped of noncerebral structures and aligned to the intercommissural line by using interactive image display software
(ANALYZE, Biodynamic Research Unit, Mayo Clinic,
Rochester, MN), were brought into the standard anatomical
space of Talairach and Tournoux [26], so that comparison
between individuals was possible using SPM software [27].
Using parameters for this transformation as a guide, the individual PET scans were brought into this normalized space
as well [28]. The PET images were smoothed with a Gaussian filter of 10 X 10 X 6 m m for individual and at 20 X
20 X 12 mm for group comparisons. The blood flow in
each voxel thus corresponded to a weighted mean rCBF centered on a spherical domain 10 mm (20 mm, respectively) in
diameter. Global flow differences between the scans were
normalized to a mean of 50 ml/dl/min by analysis of covariance with measured global flow as covariate [29]. Statistical
significant differences between conditions were assessed using
the general linear model and SPM 95 software ( p < 0.05,
corrected for multiple comparisons) [28].
The study was approved by the ethics committee. All subjects gave written informed consent to the study.
2.5
1.43
1.25
1.35
1.25
1.47
CH
IH
Threshold
Intensity
Volume
(cm’ x p,V)
IH
CH
3,934
2,002
2,009
39,018
6,212
37,638
1,666
2,040
2,045
33,997
2,267
33,985
832
1,420
1,413
8,562
2,225
8,565
27,990
5,692
27,993
12,404
21,805
12,400
2 0.44 15,929 2 15,440 5,579 ? 6,829 15,755
3,930
6,210
1,656
2,254
826
2,220
5,704
21,800
15,150 5,575
(YO)
CH
60
37
31
41
45
44
43
65
? 6,830 45.8 -t 11.3
IH
62
42
33
51
48
43
39
66
48.0 2 11.3
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( p < 0.05)
( p = 0.16)
*
( p = 0.16)
( p = 0.17)
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Individual values and average results of area, quotient, sum of amplitude, volume, and threshold intensity after transcranial magnetic stimulation
mapping of patients with facial palsy. Values are given for contralateral (CH) and ipsilateral hemisphere (IH) with respect to the facial palsy. Patients
4-8 also participated in the positron emission tomography study.
Rijntjes et al: Reorganization in Facial Palsy
623
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”””1111
1111
palsy (grades 3 and 4 ) showed a significant lateralization of the COG contralateral to the facial palsy ( p =
0.037), whereas this was not found in patients with
discrete symptoms (Table 3 ) .
Therefore, the whole patient group only showed a
nonsignificant trend of COG lateralization. A trend,
but no significant increase, was observed for the sum of
amplitudes and volume, mainly because of the large
standard deviation. Threshold intensity showed a trend
but no significant decrease over the contralateral hemisphere. The subgroup of 5 patients that also took part
in the PET investigation showed identical statistical results concerning area size, ratios, COGS,sum of amplitudes, volume, and threshold intensities.
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Positron Emission Tomogvdphy
In the normal subjects as a group,
rCBF increased in the contralateral hand field of the
SMC during fractionated finger movements, as was expected, with the center of activation at 52 mm above
the AC-PC line, ranging from 40 to 60 mm (Table 4).
The supplementary motor area (SMA) in the medial
premotor cortex was activated from 44 to 52 mm,
which is in line with previous PET studies [ 3 , 251 (Fig
2). The patients as a group activated the contralateral
SMC to a much larger extent compared with the control subjects when the hand ipsilateral to the facial
palsy was moved, including both the hand representation and part of the presumed face representation
(range, 20-52 mm) (Fig 3). Two peaks of rCBF increases were found, at 44 and at 32 mm, respectively.
The size of activation in the SMC in patients, calculated as the number of voxels, was 1.5 times the size of
activation in the control group. Direct comparison between the two groups showed the larger part of this
difference benveen 20 and 48 mm above the intercommissural line, centered around the maximum at 36
GROUP RESULTS.
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Fig 1. Areas on the scalp in the group of patients with facial
palsy fiom whom motor-evoked potentials could be recorded
fiom the contralateral hand. CH = contralateral hemisphere;
IH = ipsilateral hemisphere. One black square represents I
cm2, measured f ; o m the vertex (cross).
Results
Ttznscruniul Magnetic Stimulation
In the healthy subjects, the mean area ratio (left hemisphere/right hemisphere) was 1.01 ? 0.08. Considering 2.5 SD as a range of normal values, 6 of 8 patients
showed a ratio beyond this limit, thus indicating an
enlargement of the area contralateral to the facial palsy.
This result was statistically significant for the group of
patients (Table 2). The enlargement extended in a lateral direction (Fig 1). When comparing the COGSover
both hemispheres, patients with a more severe facial
Table 3. Results of Transcranial Magnetic Stimulation (Center
COG: Contralateral Hemisphere
..
~
_
_
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Gravity (COG])
of
~
~
COG:Ipsilateral Hemisphere
_
_
_
~
Patient
x Coordinate
y Coordinate
x Coordinate
y Coordinate
5
7
1.76
-2.42
1.54
I .04
0.32
2.04
-2.15
-0.92
-0.29
1.64
5.24
7.55
5.26
7.69
5.54
6.1
6.06
4.85
6.04
1.00
-1.8
-0.12
1.05
0.1
-0.3
1.32
-1.04
-0.68
-0.18
0.97
6.14
5.76
2.93
5.43
3.9
6.74
6.3
5.87
5.38
1.22
2
4
6
1
3
8
Mean
SD
-
Grade“
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Center of gravity (COG)is given in x a n d y coordinates for the contralateral and ipsilateral hemisphere with respect to the facial palsy.
“Grade: Grade of the facial palsy according to House and Brackman [23] (see Table 1). For explanation see text.
624
Annals of Neurology
Vol 41
No 5
May 1997
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Table 4. Results of the PET Study (Group Study)
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Normals
Patients
X
Contralateral
SMC
-40
-46
-24
-56
-8
Range: 20-52
Size: 1,397
36
-20
Range: 20-52
44
32
9.40
6.65
48
6.13
-40
-38
48
10.06
-8
-6
48
-60
-2
28
6.49
6.41
-32
-68
-2
32
48
36
4.88
5.03
5.53
z Score
x
-22
52
9.74
Ipsilateral
-2
z Score
z
Range: 40-60
Size: 984
SMC
Contralateral
BA 40
BA 7
SMA
BA 6
z
Y
-4
48
5.20
Y
Patients vs Normals
Y
z
z Score
-10
36
6.42
Range: 20-48
Size: 572
34
-24
Range: 20-48
48
5.43
-44
-22
40
48
7.0 1
4.75
24
4.33
44
44
32
3.38
4.46
4.36
x
-
-
52
-40
-68
62
2
Ipsilateral
BA 40
BA 7
BA 6
58
22
54
32
22
56
-52
-68
-4
Brain regions with changes in regional blood flow in the comparison of fractionated finger movement against rest in the control group, in
patients with facial palsy and in patients as compared with the control group are reported as coordinates ( y z ) in the standard stereotactic space
[26] with corresponding z scores. Range is in millimeters above the intercommissural line. Size is number of significant voxels in the contralateral sensorimotor cortex accivared by the task.
PET = positron emission tomography; SMC = sensorimotor cortex; BA 40 = parietal association cortex; BA 7
cortex; SMA = supplementary motor area; BA 6 = lateral premotor cortex.
mm. Ipsilateral SMC showed significant increases as
well, with an enlargement (20-52 mm) similar to that
in the contralateral SMC, but with the maximum more
rostrally (48 mm). There were strong increases in bilateral parietal association areas (Brodmann area [BA]
40), SMA, lateral premotor cortex (BA 6 ) , and in ipsilateral posterior parietal cortex (BA 7). The increases
in both the contralateral SMC ( 2 0 4 4 mm) and the
=
posterior parietal association
ipsilateral SMC (20-48 mm), in the contralateral lateral premotor cortex (BA 6) and in the bilateral parietal
association area (BA 40), were significantly stronger in
patients than in the controls in a direct group-to-group
comparison in amplitude as well as extent.
T o exclude the possibility that the variances in the
rest states in the normal subjects was greater than those
of the patients, making it easier to reach a significant
Fig 2. Projection of statistically sign;ficant areas measured with positron emission tomography during righthanded finger opposition j o m the group of normal
volunteers on transparent sagittal, coronal, and transverse views of the normalized brain.
Rijntjes et al: Reorganization in Facial Palsy
625
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Fig 3. Projection of statistically signijcant areas measured with positron emission tomography during righthandedjnger opposition fiom the group of patients
with right-sided facial pahy on transparent sagittal,
coronal, and trunsverse views of the normalized brain,
showing h e r d extension of the activation in the sensorimotor cortex and additional activation of secondary sensorimotor areas.
activation in the patients, a post hoc comparison of rest
states between the group of patients and healthy subjects for significant voxels was performed. The result
showed that the variances were not greater in the rest
states of the normal subjects than in the patients.
INDIVIDUAI. PATIENTS. In Patient 9, who was examined 7 days after the onset of facial palsy, activation in
the contralateral SMC was found in the normal hand
field (Table 5). However, in each of the other patients,
studied as single subjects, the activation consistently ex-
tended laterally, down to 24 to 36 mm above the
AC-PC line (Fig 4). No relation was found between
the duration of the facial palsy (from 29 days to 36
years) in these patients and the size of the lateral extension. Patients 4 to 8 showed strong ipsilateral SMC
activation, with a wider variation in size and local maximum than the activation on the contralateral side.
Secondary motor and sensory areas showed significant
increases in activation in all but the last patient. The
strongest activation was found in contralateral BA 40.
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Table 5. Results o f the PET Study (Individual Patients)
Patient
~
Contralateral
SMC
Ipsilateral
SMC
Contralateral
BA 40
BA 7
SMA
BA 6
lpsilateral
BA 40
BA 7
BA 6
Y
z
z Score
x
-48
-20
Range: 32-56
30
-34
Range: 32-56
48
3.60
52
4.40
-46
-20
Range: 28-64
30
-18
Range: 48-68
-34
48
5.22
Y
X
-38
38
-66
40
3.96
44
-12
44
4.11
-34
-30
-6
-34
24
26
~~
No. 6
No. 5
No. 4
z
z Score
x
56
5.36
56
3.76
-32
-56
-4
-6
44
56
64
60
5.12
4.23
5.27
5.66
-72
-12
52
48
4.67
4.57
Y
Score
z
z
-48
-18
Range: 32-48
52
-6
Range: 20-44
36
5.30
28
4.14
-38
-32
44
3.64
-50
-10
40
4.18
-6
32
4.27
56
Brain regions with changes in regional blood flow in the comparison of fractionated finger movement against rest in the individual patients are
millimeters above the intercommissural line.
PET
626
=
positron emission tomography; SMC = sensorimocor cortex; BA 40
Annals of Neurology
Vol 41
No 5
May 1997
=
parietal association cortex; BA 7
=
posterior parietal association
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Other secondary areas included lateral premotor cortex
and BA 7 bilaterally, and SMA contralaterally. All
these differences were significant when compared with
the group of control subjects.
Discussion
Patients with facial palsy activate a larger part of the
cortex than normal volunteers when making fractionated finger movements, as measured with PET, and
potentials of the abductor pollicis brevis muscle can be
elicited from a larger part of the contralateral than
from the ipsilateral cortex after TMS. The most striking finding was a lateral extension of the hand area
within the contralateral SMC. However, reorganizational changes were found in other areas, eg, bilateral
secondary somatosensory areas and ipsilateral SMC.
This reorganization occurred even if the motor deefferentation was not complete, ie, in those patients with
incomplete facial palsy. With TMS mapping, the amplitude parameters revealed a trend to enhanced amplitudes over the hemisphere contralaterally to the facial
palsy. The lack of statistical significance is due to the
common large interindividual variability of TMS amplitudes 1301. Nevertheless, the combination of increased amplitudes and decreased stimulus intensities
over the hemisphere contralateral to the facial palsy indicates an enhanced excitability of this small hand
muscle motor area.
Consistent with TMS, fractionated finger movements in patients led to a larger activation in the contralateral SMC, as measured with PET. Local maxima
were found in the hand area (44 mm above the intercommissural line) and in the supposed face area (32
mm) [ l , 311. Direct comparison between patients and
normal subjects showed this additional activation to be
in the face area (36 mm). The lateral extension in this
study comprised the same area found in previous studies in recovered stroke patients with a posterior lesion
of the internal capsula, sparing the corticobulbar fibers
destined for facial movement [2O, 211, or in patients
with amyotrophic lateral sclerosis without bulbar involvement when moving the paretic hand [22].
Whereas in these latter studies the lateral extension
may reflect compensatory mechanisms to move the paretic hand, in our study the cortical representation of
the healthy limb extended into a neighboring deefferented area in an intact brain. Also, our finding is complementary to previous studies [14, 321, in which an
expansion of the face representation into the hand area
was found. However, in the latter studies a combined
sensory and motor lesion was present. Apparently, reorganizational processes in the motor cortex can occur
after central or peripheral deefferentation and deafferentation and with different underlying mechanisms. In
the heterogeneous group, neither TMS nor PET
showed a statistically significant correlation between
the duration or intensity of the facial palsies and the
extent of cortical area involved, but the lateral extension was present as early as 1 month after onset of the
facial palsy.
Animal studies provide little anatomical evidence to
support the notion that the newly recruited neurons in
the lateral extension in the SMC are somehow related
to finger movements under normal conditions, since
virtually no overlap between hand and face representations are reported. Horseradish peroxidase injections
placed in the forelimb representation of monkeys, close
to the physiologically defined face representation, re-
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Table 5. Continued
Patient
No. 7
X
Y
z
z Score
-36
-30
44
5.05
Range: 24-60
28
-14
44
-36
z
z Score
-18
48
3.97
Y
z
z Score
-46
-20
48
3.47
-
52
4.00
Range: 40-52
None
48
4.89
4.45
28
-30
x
40
Range: 40-56
52
4.52
-
36
-42
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zyxw
36
-36
48
4.30
reported as coordinates (xy.)in the standard stereotactic space of Talairach and Tournoux
SMA
Y
x
Range: 36-56
Range: 40-54
-42
No. 9
No. 8
= supplementary motor area;
[42]with corresponding z scores. Range is in cortex;
BA 6 = lateral premotor cortex.
Rijntjes et al: Reorganization in Facial Palsy
627
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Fig 4. Statistically signi$cant areas measured with positron emission tomography during right-handed finger opposition )om a normal volunteer (/&) and a patient (right, No. 7) with right-sided @cia/ palsy during right-handed finger opposition, projected on
individual three-dimensional magnetic re.tonance imaging scans, showing lateral extension of the activation in the sensorimotor cortex in the patient.
sulted in virtually no retrograde labeled cells or terminal fiber labeling that crossed into the face representation [33]. In another study on primates, digit
movemenrs could be elicited only at the medial boundary of the orofacial representation [34]. However, there
is increasing evidence that these seemingly stable representations are kept in place by powerful
y-aminobutyric acid-mediated lateral inhibitory connections that are found to interconnect cortical areas
over considerable distances [35]. Loss of these lateral
inhibitory connections could well provide a stimulus
for intracortical reorganization. Although axonal
sprouting has been observed in macaque monkeys after
long-term deafferentation [ 161, it does not explain the
rapid changes observed in animal experiments [ 171 and
in our study, in which lateral extension of the hand
area was already observed after 29 days. Studies on
lower levels of the system, where a somatopy similar to
the one in the cortex can be found, show that injuryinduced reorganization can be as complete as in the
cortex [36]. Thus, there is the possibility that cortical
reorganizations simply reflect changes already manifest
at lower levels.
All patients reported normal feeling in the paretic
face area, and the contralateral orbicularis oculi reflexes
were normal, demonstrating intact trigeminal sensory
pathways. However, since normal everyday proprioceptive information is absent due to lack of movement, or
diminished in those patients with incomplete facial
palsy, a certain amount of deafferentation must be assumed as well. A recent PET study in normal subjects
showed that proprioception constitutes the larger part
628 Annals of Neurology
Vol 41
No 5
May 1997
of [he activation seen in the SMC during a motor task
[37].Thus, deafferentation may have played a role in
our findings in patients with Bell’s palsy.
In all comparisons made in the PET study, the ipsilateral SMC showed significant activation during performance of the task. The activation was mainly in the
normal hand area, but extended downwards to 20 mm
above the AC-PC line, which is in the supposed face
area [I, 311. ‘This finding is difficult to interpret. The
peripheral facial nerve lesion should have some impact
on the ipsilateral face area, since the upper part of the
face is innervated bilaterally. In monkeys, neurons for
the ipsilateral and contralateral face in the face motor
cortex are intermingled with each other, and ipsilateral
facial movements can be elicited from 20% of the positive sites in the face motor cortex of either hemisphere
with microelectrodes [34]. Therefore, deefferentation
of one-half of the face will also deefferent partly the
ipsilateral cortex, possibly initiating the same reorganizational mechanisms that are responsible for the contralateral hand area. Additional stimuli for ipsilateral
activation could be provided by transcallosal connections. Calford and Tweedale [38] reported on interhemispheric transfer of plasticity in the somatosensory
cortex after local anesthesia of one thumb of flying
foxes, in which the extent and time course of the plasticity were mirrored in both hemispheres. There is
some evidence for an ipsilateral hand representation in
some normal subjects and this may be positioned lateroposterior to the normal hand area [21, 391. Hypothetically, lateral extension caused by deefferentation of
the face may include or overlap with this area. There
zy
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are conflicting reports in the literature whether movements with the nondominant hand are related to more
ipsilateral activation than movements with the dominant hand [40, 411. However, we cannot dismiss the
possibility that due to the mixture of dominant and
nondominant hand movements in the patient group
the results are biased toward ipsilateral activation in the
patients.
The additional activation of secondary motor and
sensory areas seems to be a common finding in studies
on cortical reorganization. A shift to modality-specific
secondary or higher order processing areas (eg, prefrontal cortex and parietal cortex) has been consistently
found in a variety of conditions with central [22,211
or peripheral [14] nervous lesions. From animal and
human studies, there is ample evidence for strong anatomical connections between the different secondary
areas, each of which contains a somatotopic representation of body parts [42].
In conclusion, our study shows for the first time
with two entirely different and noninvasive methods a
functional plasticity in the intact adult human brain in
response to mere peripheral deefferentation.
This study was supported in part by an EU grant (CT 94/1261)
and by the Kuratorium ZNS, Bonn, Germany.
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We thank the patients and volunteers for their participation, Dr. M.
Schwarz from the Neurology Department of the RWTH Aachen,
Germany, for helpful discussion, Barbel Terschiiren for help in
scanning the patients, and Marjorie Weiss for carefully proofreading
the manuscript.
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