Cortical metabolism in posterolateral thalamic stroke: PET study
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Chabriat H, Pappata S, Levasseur M, Fiorelli M, Tran Dinh S, Baron JC. Cortical metabolism in posterolateral thalamic stroke: PET study. Acta Neurol Scand 1992: 86: 285-290.
H. Chabriatl, S. Pappata’,
In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the “F-fluorodeoxyglucose or the ‘50-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the “non-specific” thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain.
Biology Department, Service Hospitalier FrbdBric Joliot, CEA, * INSERM U334, Orsay, INSERM, U 3 2 0 , Caen, France
Thalamic lesions, even of small size, often induce a metabolic depression of the entire ipsilateral cerebral cortex (1, 2, 3). This remote functional effect (diaschisis) is associated to the neuropsychological expression of thalamic stroke (1-5). Damage to the “non-specific” thalamocortical projections has been suggested to account for this phenomenon (1, 3). However, no report has specifically investigated the effects of damage to a “specific” thalamocortical system on cortical metabolism. To address this issue, we used positron emission tomography (PET) to measure cortical energy metabolism in eight consecutive patients with posterolateral thalamic stroke selected on stringent clinical and radiological criteria. Material and methods
Out of a series of 63 consecutive patients with unilateral thalamic lesion who underwent a PET study in our institution, 8 patients with posterolateral thalamic stroke (mean age = 60.5 8.8 years) were strictly selected on the following clinical and MRI criteria: 1) hemisomatosensory impairment and/or pain on one side of the body; 2) lack of significant motor deficit at time of PET study; 3) MRI evidence of a unilateral, predominantly thalamic lesion affecting the posterolateral thalamus on the side opposite to the clinical symptoms and/or signs; 4) neuropsychological assessment within normal limits to concur with literature reports about posterolateral tha-
’,
’,
M. Levasseur M. Fiorelli S. Tran Dinh’, J. C. Baron3
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Key words: cerebrovascular disease; thalamus; pain; diaschisis J.C. Baron, INSERM U 3 2 0 , CYCERON, BP 5027, 1 4 0 2 1 Caen Cedex, France
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Accepted for publication January 22, 1992
lamic stroke (6-9); and 5) lack of detectable cortical lesions on MRI. Delay from onset of stroke to PET study ranged from 10 days to 9 years. Forty-six unmedicated subjects free from cerebrovascular risk factors or previous neurologic or psychiatric disease were used as controls. MRI
Proton MRI was performed with a superconducting General Electric Imager (field strength of 1.5 tesla). Seven to nine sections (5 mm thick) were acquired in all patients, completed by additional coronal and/or sagittal cuts. T1-weighted images using partial saturation sequence (TR = 500-600 msec and TE = 25 msec) and TZweighted images with spin echo sequence (TR = 2000-2500 msec and TE = 4080-90 msec) were obtained. The interval between MRI and PET studies ranged from 1 to 20 days. PET
PET studies of regional metabolic rate of either oxygen (CMR02) or glucose (CMRGlu) - which are similarly reduced in deafferented areas (1, 10) - were performed using the C’502-’50, continuous inhalation technique (without correction for intravascular tracer compartment) or the ‘8F-Fluoro-2-deoxyglucose ( 18FDG)“in vivo autoradiographic” method, respectively. The CMRO, and the CMRGlu were 285
Chabriat et al. measured in 5 and 3 patients, respectively. The methods relative to 18FDG and 1 5 0 , as applied in our center have been described in detail in previous reports (1 1, 12). The positron tomograph used was the seven slice LET1 time of flight TTVOl system; both slice thickness and lateral resolution were 13 mm (13). Correction for attenuation was carried out using 68Ge-68Gatransmission scans. The studies were performed with the subjects at rest, with their eyes closed but ears unplugged, and in a quiet and dimly lit environment. Four direct and 3 cross planes parallel to the orbitometal line (OM) were acquired at standardized brain levels. Three typical brain planes, corresponding to the “basal ganglia cut” (OM + 40 mm), the “low centrum semi-ovale cut” (OM + 55 mm), and the “high centrum semiovale cut” (OM + 70 mm), were selected out of the 7 original ones. On each of these planes, circular regions of interest (ROIs) of 3 cm2 area were positioned along the cortical rim tangentially to each other and to an external isocontour of 30% of maximal pixel activity, according to a standardized procedure (14). For each patient, the average cortical metabolic rate ipsilateral and contralateral to the thalamic lesion was calculated by combining ROI data from the three selected planes. In addition, out of the above-defined ROIs, three ROIs encompassing the sensorimotor (SM) area (15) were carefully selected on each side of the cortical mantle, on planes OM + 55 cm (one ROI) and O M + 70 mm (two tan-
gential ROIs) in accordance with the atlas of Matsui and Hirano (16) and with reference to the anatomical correlations for imaging systems reported by Salamon et al. (17). SM area as defined by this method included the middle inferior part of Brodmann’s areas 1, 2, 3, 4, and 6 (18). The regional metabolic rate for the SM area was calculated by averaging the values from these three selected ROIs. Statistical analysis
In each patient, the absolute metabolic rates of the whole cortex and SM cortex were calculated separately for the sides ipsilateral and contralateral to the thalamic lesion. To account for different PET methods (i.e. C M R 0 2 or CMRGlu) the metabolic data were normalized using a validated method (19). In brief, for each type of PET study (CMRO, or CMRGlu), a regression line of the cortical metabolic measures versus age was calculated in the control group (CMRO,, n = 15; CMRGlu, n = 3 1). The value for each subject (i.e., patient or control), was subsequently divided by the corresponding predicted value for the subject’s age using regression lines specific to the region under consideration, the type of PET study and the brain side. This normalization procedure was applied to the absolute metabolic rates of the whole cortex and of the sensorimotor cortex. We used asymmetry indexes of normalized metabolic values derived as [ (ipsilateral - contra-
Fig. 1 . T1 (patients # 3, 4, 7, 8) and T2 ( # 1, 2, 5 , 6 ) weighted MRI images best showing the unilateral posterolateral thalamic lesion. In addition to the increased signal intensity area in the thalamus (10 day-old hemorrhage), the T1 image in patient # 4 shows bilateral putaminal areas of decreased signal intensity, which presumably reflect dilated perivascular spaces (22,24).
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Cortical metabolism & thalamic stroke Table 1. Clinical features in patients Clinical findings at pet time Sensory deficit Patient age sex
Lesion type
Anamnestic clinical data
Delay
Pain
Touch
Pain
Temperature
Position vibratory sense
Spontaneous dysesthesia
Hyperpathic overreaction
Ataxia
Choreoathetosis
Altered cortical SEP
1/72/F
Hemidysesthesia hemihypoesthesia hemiparesis hemiataxia
10 d
t
t
t
t
t
-
t
t
nd
2/65/F
hemihypoesthesia hemiparesis burning pain hyperpathy
3Y
t
t
t
t
t
t
-
-
nd
3/53/F
hemidysesthesia hemihypoesthesia hemiparesis
1.5 y
4/59/M
hemidysesthesia hemihypoesthesia
10 d
t
515 1/F
hemidysesthesia hemihypoesthesia hemiparesis hemiataxia
60 d
nd
6/76/F
hemidysesthesia hemihypoesthesia hemiparesis hyperpathy hemiataxia
19 d
7/6O/F
hemihypoesthesia hemiparesis burning pain hemiataxia
9Y
nd
8/72/F
hemidysesthesia hemiataxia
3y
-
t
t
t
t
-
t
t
t
-
t
Delay=time elapsed between stroke and PET study, I=lnfarct, Hthemorrhage, y=years, SEP=somatosensory evoked potentials, (+)=impairment present, (-)=no impairment, nd=not done.
lateral)/contralateral] in patients and as [(right left)/left] in controls (19); this was possible because there is no statistically significant systematic asymmetry of these indexes in the control population (20). The means of the absolute values and of the asymmetry indexes obtained in patients were compared with those obtained in controls using Student tTests. Similarly, the mean ipsilateral [sensorimotor/ whole cortex] ratio calculated in patients was compared to the right and left [ sensorimotor/whole cortex] ratios obtained in controls. Computation of the correlation between time from stroke onset and the normalized metabolic data was also performed, using Pearson’s linear regression method. Results
In each patient, the MRI (Fig. 1) showed a unilateral posterolateral thalamic lesion (infarct in 5 pa-
tients and hemorrhage in 3). The lesion was leftsided in 3 ( # 3, 6, 8) and right-sided in 5 ( # 1, 2, 4, 5,7) patients. In one patient with hemorrhage ( # 2), the lesion slightly extended to the neighboring internal capsule (posterior limb). The MRI also revealed a contralateral striatal lesion in patient # 3 and a punctate contralateral thalamic lesion in patient # 4. Minor MRI abnormalities similar to those frequently identified in the elderly were observed in 3 patients, consisting of patchy periventricular foci of T2 increased signal intensity (21) ( # 2, 4, s), and low T1 and high T2 signal in the lateral putamen presumably corresponding to dilated perivascular spaces (22-24) ( # 4). The clinical data are shown in Table 1. Six patients could be classified as Dejerine and Roussy syndrome (25,26) ( # 1,2,3,5,6,7) and two as pure sensory stroke (27) ( # 4, 8); both syndromes are known to result from damage to the posterolateral 281
Chabriat et al.
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Fig. 2. Mean ( f SD) normalized metabolic rates for right and left whole cortex of 46 controls and individual and mean ( f SD) whole cortex values for the sides ipsilateral and contralateral to posterolateral thalamic lesion in patients. The lines join the ipsilateral and contralateral values obtained in individual patients. There is no statistically significant changes in patients compared to controls.
thalamus (26-28). In all patients, the visual field was normal. The neuropsychological assessment, performed at time of PET study, was based on a standard assessment: all patients were well oriented in time and space; verbal fluency, verbal comprehension, naming and reading was normal; writing on dictation was unimpaired; evocation of recent or remote events was correct; and spontaneous drawing of a cube and executing sequential geometrical figures showed no significantly abnormality. The absolute normalized metabolic data are shown in Figs. 2 and 3. Statistical analysis showed no significant difference between patients and controls for the mean absolute normalized cortical metabolic rates (whole cortex and sensorimotor cortex), both
Irn -
4
K -
,
Y (*
8
m-
1 - Fig. 3. Mean ( & SD) normalized metabolic rates for right and left sensorimotor cortex of 46 controls and individual and mean ( f SD) sensorimotor cortex values for the sides ipsilateral and contralateral to posterolateral thalamic lesion in patients. The lines join the ipsilateral and contralateral values obtained in individual patients. There is no statistically significant changes in patients compared to controls.
288
ipsilateral and contralateral to the thalamic lesion. Similarly, no significant difference was found for the mean metabolic asymmetry indexes of the whole cortex ( - 1.4 & 7% in patients; 0.1 k 2.8% in controls; p = 0.27) and sensorimotor cortex ( - 3.2 k 6.2% in patients; 0.4 4 7.4% in controls: p = 0.19). In addition, the mean ipsilateral [ sensorimotor/whole cortex] ratio of normalized values in patients did not significantly differ from the corresponding left or right ratios obtained in controls (1.04 & 0.09 vs 1.00 & 0.06 and 1.00 k 0.07, respectively). No significant correlation was found between delay from stroke onset to PET study and normalized absolute cortical metabolic data or metabolic indexes. Comparison of the normalized data according to recent (10-60 days, patients # 1,4, 5, 6) and old (1.5-9 years, patients # 2, 3, 7, 8) stroke groups showed no significant difference by t-tests. Discussion
Our results show that the ipsilateral cortical hypometabolism (ICH), characteristic of thalamic lesions (1, 19) is not found in posterolateral thalamic stroke. In previous studies, cortical metabolic effects were observed regardless of the exact topography or size of the thalamic lesion (1,29), including stereotaxic lesions limited to part of the ventro-lateral (ViM) nucleus; however, Baron et al. (1) originally pointed out the lack of ICH in one patient with posterolatera1 thalamic infarction. Thus, our data support the hypothesis that location of the thalamic lesion plays a key role in the occurrence of ICH. In the present work, we selected the patients for their normal neuropsychological function. At variance with medial or anterior thalamic lesions which often induce impairment of consciousness or cognitive function (7, 9) patients with small lesions of the posterolateral thalamus are usually spared of such effects (6, 7). Previous PET and single photon emission tomography (SPECT) studies have suggested a close association between cognitive deficit and diffuse cortical metabolic depression (1, 3, 5, 19). By the negative nature of its findings, the present study further supports this link between cognitive status and cortical metabolism in thalamic lesions and is consistent with earlier findings of normal cortical metabolism in cognitively unaffected patients with internal capsule (posterior limb) stroke (19). Damage to the so called “non-specific” thalamocortical system has been implicated to account for metabolic effects on the entire ipsilateral cortical mantle secondary to circumscribed thalamic lesions (1, 19). The role played by the “non-specific” thalamic nuclei in the neocortical activation is well established (30-33). In support, specific lesions of the
Cortical metabolism & thalamic stroke ventro-medial thalamic nucleus (which is part of the “non-specific’’ system) in rats also result in cortical hypometabolism (34). In our patients, the clinical and MRI data suggest that the ventroposterolateral nucleus (VPL) was the single consistently injured thalamic nucleus while intralaminar and other “nonspecific” thalamic nuclei clearly were less consistently involved (7-9). At variance with the essentially diffuse cortical projections of the “non-specific” thalamic nuclei, the cortical projections of the VPL terminate with a coherent topographic ordering within the SM cortex (15, 35). Thus, somatosensory stimulations in humans increase blood flow and metabolism in the contralateral SM cortex (36) and electric stimulation of the VPL in both humans and rats results in metabolic activation in the SM area (37,38). In addition, numerous experimental findings have established that the specific cortical projections are anatomically and functionally independent from the non-specific system (31, 32, 35, 3941). Hence, the lack of diffuse ICH in our study further emphasizes the major impact of the non specific thalamo-cortical system on resting cortical metabolism. More unexpectedly, we did not observe a significant metabolic depression over the SM cortex ipsilateral to the thalamic lesion; this is consistent with the report of normal cortical metabolism before stimulation in five patients with VPL implants for intractable peripheral deaerentation pain (37). Several factors could explain these negative results. First, the SM cortex is topographically limited and hence its sampling in resting PET studies is somewhat uncertain. Second, the sensory impairment in our patients was often incomplete, indicating only partial SM deafFerentation. In support, 3 of our 4 patients tested had abnormal cortical somatosensory evoked potentials (SEPs) N20 or P25 waves (42), but they were normal in one patient with pure sensory stroke ( # 8), indicating limited damage to the VPL thalamocortical pathway (43, 44). Finally, recovery from initial metabolic impairment can be one confounding factor (49, but we found no significant relationship between times since onset of stroke and PET data. In the rat, the somatosensory cortex glucose use normalized in less than 2 weeks after the removal of whiskers (46). The apparent lack of metabolic effects in the SM area in our patients must be considered in the light of the clinical impairment, which was prominent in all. Hence, 7/8 patients had some degree of thalamic pain (26,47) including patients # 8 with pure sensory stroke at PET time. Our results suggesting that cortical metabolism is unaltered in patients with thalamic pain agree with Laterre et al. who also found normal cortical metabolism in one patient suffering from “thalamic” pain after a small internal capsular
infarction (48). The hypothesis that hyperactivity of intralaminar thalamic nuclei may be implicated in thalamic pain has been previously formulated (48,50). A role for the cerebral cortex as the main relay of inhibition upon the intralaminar thalamic nuclei remains debated (49); however the lack of prominent cortical hypometabolism in our subjects would support the hypothesis that the loss of intralaminar nuclei inhibition originates at the subcortical, and not at the cortical level. Yet, cortical metabolic activation secondary to hyperactivity of the intralaminar nuclei, if any, could account for the lack of detectable reduction in cortical metabolism. Acknowledgement The authors wish to thank B. Mazoyer MD, PhD, for his helpful advice on statistical analysis.
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Chabriat H, Pappata S, Levasseur M, Fiorelli M, Tran Dinh S, Baron JC. Cortical metabolism in posterolateral thalamic stroke: PET study. Acta Neurol Scand 1992: 86: 285-290.
H. Chabriatl, S. Pappata’,
In 8 patients with small unilateral posterolateral thalamic (or, in one case, thalamocapsular) stroke (infarction or hemorrhage) selected on strict clinical (pure hemisomatosensory deficit without hemiparesis, visual field defect or neuropsychological impairment) and MRI criteria, we studied cortical energy metabolism using positron emission tomography with the “F-fluorodeoxyglucose or the ‘50-oxygen method. We found no significant ipsi- or contra-lateral metabolic depression either in the whole cortical mantle or in the sensorimotor cortex. These results support the hypothesis that location of thalamic stroke is a major determinant of the ipsilateral cortical hypometabolism characteristic of cognitively impaired patients with thalamic lesions and further emphasize the influence of the “non-specific” thalamocortical system on resting cortical metabolism. The lack of sensorimotor cortex hypometabolism in our patients suffering from hemidysesthesia and/or -hyperpathia also suggests that cortical metabolism is unaltered in thalamic pain.
Biology Department, Service Hospitalier FrbdBric Joliot, CEA, * INSERM U334, Orsay, INSERM, U 3 2 0 , Caen, France
Thalamic lesions, even of small size, often induce a metabolic depression of the entire ipsilateral cerebral cortex (1, 2, 3). This remote functional effect (diaschisis) is associated to the neuropsychological expression of thalamic stroke (1-5). Damage to the “non-specific” thalamocortical projections has been suggested to account for this phenomenon (1, 3). However, no report has specifically investigated the effects of damage to a “specific” thalamocortical system on cortical metabolism. To address this issue, we used positron emission tomography (PET) to measure cortical energy metabolism in eight consecutive patients with posterolateral thalamic stroke selected on stringent clinical and radiological criteria. Material and methods
Out of a series of 63 consecutive patients with unilateral thalamic lesion who underwent a PET study in our institution, 8 patients with posterolateral thalamic stroke (mean age = 60.5 8.8 years) were strictly selected on the following clinical and MRI criteria: 1) hemisomatosensory impairment and/or pain on one side of the body; 2) lack of significant motor deficit at time of PET study; 3) MRI evidence of a unilateral, predominantly thalamic lesion affecting the posterolateral thalamus on the side opposite to the clinical symptoms and/or signs; 4) neuropsychological assessment within normal limits to concur with literature reports about posterolateral tha-
’,
’,
M. Levasseur M. Fiorelli S. Tran Dinh’, J. C. Baron3
’
Key words: cerebrovascular disease; thalamus; pain; diaschisis J.C. Baron, INSERM U 3 2 0 , CYCERON, BP 5027, 1 4 0 2 1 Caen Cedex, France
I
Accepted for publication January 22, 1992
lamic stroke (6-9); and 5) lack of detectable cortical lesions on MRI. Delay from onset of stroke to PET study ranged from 10 days to 9 years. Forty-six unmedicated subjects free from cerebrovascular risk factors or previous neurologic or psychiatric disease were used as controls. MRI
Proton MRI was performed with a superconducting General Electric Imager (field strength of 1.5 tesla). Seven to nine sections (5 mm thick) were acquired in all patients, completed by additional coronal and/or sagittal cuts. T1-weighted images using partial saturation sequence (TR = 500-600 msec and TE = 25 msec) and TZweighted images with spin echo sequence (TR = 2000-2500 msec and TE = 4080-90 msec) were obtained. The interval between MRI and PET studies ranged from 1 to 20 days. PET
PET studies of regional metabolic rate of either oxygen (CMR02) or glucose (CMRGlu) - which are similarly reduced in deafferented areas (1, 10) - were performed using the C’502-’50, continuous inhalation technique (without correction for intravascular tracer compartment) or the ‘8F-Fluoro-2-deoxyglucose ( 18FDG)“in vivo autoradiographic” method, respectively. The CMRO, and the CMRGlu were 285
Chabriat et al. measured in 5 and 3 patients, respectively. The methods relative to 18FDG and 1 5 0 , as applied in our center have been described in detail in previous reports (1 1, 12). The positron tomograph used was the seven slice LET1 time of flight TTVOl system; both slice thickness and lateral resolution were 13 mm (13). Correction for attenuation was carried out using 68Ge-68Gatransmission scans. The studies were performed with the subjects at rest, with their eyes closed but ears unplugged, and in a quiet and dimly lit environment. Four direct and 3 cross planes parallel to the orbitometal line (OM) were acquired at standardized brain levels. Three typical brain planes, corresponding to the “basal ganglia cut” (OM + 40 mm), the “low centrum semi-ovale cut” (OM + 55 mm), and the “high centrum semiovale cut” (OM + 70 mm), were selected out of the 7 original ones. On each of these planes, circular regions of interest (ROIs) of 3 cm2 area were positioned along the cortical rim tangentially to each other and to an external isocontour of 30% of maximal pixel activity, according to a standardized procedure (14). For each patient, the average cortical metabolic rate ipsilateral and contralateral to the thalamic lesion was calculated by combining ROI data from the three selected planes. In addition, out of the above-defined ROIs, three ROIs encompassing the sensorimotor (SM) area (15) were carefully selected on each side of the cortical mantle, on planes OM + 55 cm (one ROI) and O M + 70 mm (two tan-
gential ROIs) in accordance with the atlas of Matsui and Hirano (16) and with reference to the anatomical correlations for imaging systems reported by Salamon et al. (17). SM area as defined by this method included the middle inferior part of Brodmann’s areas 1, 2, 3, 4, and 6 (18). The regional metabolic rate for the SM area was calculated by averaging the values from these three selected ROIs. Statistical analysis
In each patient, the absolute metabolic rates of the whole cortex and SM cortex were calculated separately for the sides ipsilateral and contralateral to the thalamic lesion. To account for different PET methods (i.e. C M R 0 2 or CMRGlu) the metabolic data were normalized using a validated method (19). In brief, for each type of PET study (CMRO, or CMRGlu), a regression line of the cortical metabolic measures versus age was calculated in the control group (CMRO,, n = 15; CMRGlu, n = 3 1). The value for each subject (i.e., patient or control), was subsequently divided by the corresponding predicted value for the subject’s age using regression lines specific to the region under consideration, the type of PET study and the brain side. This normalization procedure was applied to the absolute metabolic rates of the whole cortex and of the sensorimotor cortex. We used asymmetry indexes of normalized metabolic values derived as [ (ipsilateral - contra-
Fig. 1 . T1 (patients # 3, 4, 7, 8) and T2 ( # 1, 2, 5 , 6 ) weighted MRI images best showing the unilateral posterolateral thalamic lesion. In addition to the increased signal intensity area in the thalamus (10 day-old hemorrhage), the T1 image in patient # 4 shows bilateral putaminal areas of decreased signal intensity, which presumably reflect dilated perivascular spaces (22,24).
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Cortical metabolism & thalamic stroke Table 1. Clinical features in patients Clinical findings at pet time Sensory deficit Patient age sex
Lesion type
Anamnestic clinical data
Delay
Pain
Touch
Pain
Temperature
Position vibratory sense
Spontaneous dysesthesia
Hyperpathic overreaction
Ataxia
Choreoathetosis
Altered cortical SEP
1/72/F
Hemidysesthesia hemihypoesthesia hemiparesis hemiataxia
10 d
t
t
t
t
t
-
t
t
nd
2/65/F
hemihypoesthesia hemiparesis burning pain hyperpathy
3Y
t
t
t
t
t
t
-
-
nd
3/53/F
hemidysesthesia hemihypoesthesia hemiparesis
1.5 y
4/59/M
hemidysesthesia hemihypoesthesia
10 d
t
515 1/F
hemidysesthesia hemihypoesthesia hemiparesis hemiataxia
60 d
nd
6/76/F
hemidysesthesia hemihypoesthesia hemiparesis hyperpathy hemiataxia
19 d
7/6O/F
hemihypoesthesia hemiparesis burning pain hemiataxia
9Y
nd
8/72/F
hemidysesthesia hemiataxia
3y
-
t
t
t
t
-
t
t
t
-
t
Delay=time elapsed between stroke and PET study, I=lnfarct, Hthemorrhage, y=years, SEP=somatosensory evoked potentials, (+)=impairment present, (-)=no impairment, nd=not done.
lateral)/contralateral] in patients and as [(right left)/left] in controls (19); this was possible because there is no statistically significant systematic asymmetry of these indexes in the control population (20). The means of the absolute values and of the asymmetry indexes obtained in patients were compared with those obtained in controls using Student tTests. Similarly, the mean ipsilateral [sensorimotor/ whole cortex] ratio calculated in patients was compared to the right and left [ sensorimotor/whole cortex] ratios obtained in controls. Computation of the correlation between time from stroke onset and the normalized metabolic data was also performed, using Pearson’s linear regression method. Results
In each patient, the MRI (Fig. 1) showed a unilateral posterolateral thalamic lesion (infarct in 5 pa-
tients and hemorrhage in 3). The lesion was leftsided in 3 ( # 3, 6, 8) and right-sided in 5 ( # 1, 2, 4, 5,7) patients. In one patient with hemorrhage ( # 2), the lesion slightly extended to the neighboring internal capsule (posterior limb). The MRI also revealed a contralateral striatal lesion in patient # 3 and a punctate contralateral thalamic lesion in patient # 4. Minor MRI abnormalities similar to those frequently identified in the elderly were observed in 3 patients, consisting of patchy periventricular foci of T2 increased signal intensity (21) ( # 2, 4, s), and low T1 and high T2 signal in the lateral putamen presumably corresponding to dilated perivascular spaces (22-24) ( # 4). The clinical data are shown in Table 1. Six patients could be classified as Dejerine and Roussy syndrome (25,26) ( # 1,2,3,5,6,7) and two as pure sensory stroke (27) ( # 4, 8); both syndromes are known to result from damage to the posterolateral 281
Chabriat et al.
d
I
I
Fig. 2. Mean ( f SD) normalized metabolic rates for right and left whole cortex of 46 controls and individual and mean ( f SD) whole cortex values for the sides ipsilateral and contralateral to posterolateral thalamic lesion in patients. The lines join the ipsilateral and contralateral values obtained in individual patients. There is no statistically significant changes in patients compared to controls.
thalamus (26-28). In all patients, the visual field was normal. The neuropsychological assessment, performed at time of PET study, was based on a standard assessment: all patients were well oriented in time and space; verbal fluency, verbal comprehension, naming and reading was normal; writing on dictation was unimpaired; evocation of recent or remote events was correct; and spontaneous drawing of a cube and executing sequential geometrical figures showed no significantly abnormality. The absolute normalized metabolic data are shown in Figs. 2 and 3. Statistical analysis showed no significant difference between patients and controls for the mean absolute normalized cortical metabolic rates (whole cortex and sensorimotor cortex), both
Irn -
4
K -
,
Y (*
8
m-
1 - Fig. 3. Mean ( & SD) normalized metabolic rates for right and left sensorimotor cortex of 46 controls and individual and mean ( f SD) sensorimotor cortex values for the sides ipsilateral and contralateral to posterolateral thalamic lesion in patients. The lines join the ipsilateral and contralateral values obtained in individual patients. There is no statistically significant changes in patients compared to controls.
288
ipsilateral and contralateral to the thalamic lesion. Similarly, no significant difference was found for the mean metabolic asymmetry indexes of the whole cortex ( - 1.4 & 7% in patients; 0.1 k 2.8% in controls; p = 0.27) and sensorimotor cortex ( - 3.2 k 6.2% in patients; 0.4 4 7.4% in controls: p = 0.19). In addition, the mean ipsilateral [ sensorimotor/whole cortex] ratio of normalized values in patients did not significantly differ from the corresponding left or right ratios obtained in controls (1.04 & 0.09 vs 1.00 & 0.06 and 1.00 k 0.07, respectively). No significant correlation was found between delay from stroke onset to PET study and normalized absolute cortical metabolic data or metabolic indexes. Comparison of the normalized data according to recent (10-60 days, patients # 1,4, 5, 6) and old (1.5-9 years, patients # 2, 3, 7, 8) stroke groups showed no significant difference by t-tests. Discussion
Our results show that the ipsilateral cortical hypometabolism (ICH), characteristic of thalamic lesions (1, 19) is not found in posterolateral thalamic stroke. In previous studies, cortical metabolic effects were observed regardless of the exact topography or size of the thalamic lesion (1,29), including stereotaxic lesions limited to part of the ventro-lateral (ViM) nucleus; however, Baron et al. (1) originally pointed out the lack of ICH in one patient with posterolatera1 thalamic infarction. Thus, our data support the hypothesis that location of the thalamic lesion plays a key role in the occurrence of ICH. In the present work, we selected the patients for their normal neuropsychological function. At variance with medial or anterior thalamic lesions which often induce impairment of consciousness or cognitive function (7, 9) patients with small lesions of the posterolateral thalamus are usually spared of such effects (6, 7). Previous PET and single photon emission tomography (SPECT) studies have suggested a close association between cognitive deficit and diffuse cortical metabolic depression (1, 3, 5, 19). By the negative nature of its findings, the present study further supports this link between cognitive status and cortical metabolism in thalamic lesions and is consistent with earlier findings of normal cortical metabolism in cognitively unaffected patients with internal capsule (posterior limb) stroke (19). Damage to the so called “non-specific” thalamocortical system has been implicated to account for metabolic effects on the entire ipsilateral cortical mantle secondary to circumscribed thalamic lesions (1, 19). The role played by the “non-specific” thalamic nuclei in the neocortical activation is well established (30-33). In support, specific lesions of the
Cortical metabolism & thalamic stroke ventro-medial thalamic nucleus (which is part of the “non-specific’’ system) in rats also result in cortical hypometabolism (34). In our patients, the clinical and MRI data suggest that the ventroposterolateral nucleus (VPL) was the single consistently injured thalamic nucleus while intralaminar and other “nonspecific” thalamic nuclei clearly were less consistently involved (7-9). At variance with the essentially diffuse cortical projections of the “non-specific” thalamic nuclei, the cortical projections of the VPL terminate with a coherent topographic ordering within the SM cortex (15, 35). Thus, somatosensory stimulations in humans increase blood flow and metabolism in the contralateral SM cortex (36) and electric stimulation of the VPL in both humans and rats results in metabolic activation in the SM area (37,38). In addition, numerous experimental findings have established that the specific cortical projections are anatomically and functionally independent from the non-specific system (31, 32, 35, 3941). Hence, the lack of diffuse ICH in our study further emphasizes the major impact of the non specific thalamo-cortical system on resting cortical metabolism. More unexpectedly, we did not observe a significant metabolic depression over the SM cortex ipsilateral to the thalamic lesion; this is consistent with the report of normal cortical metabolism before stimulation in five patients with VPL implants for intractable peripheral deaerentation pain (37). Several factors could explain these negative results. First, the SM cortex is topographically limited and hence its sampling in resting PET studies is somewhat uncertain. Second, the sensory impairment in our patients was often incomplete, indicating only partial SM deafFerentation. In support, 3 of our 4 patients tested had abnormal cortical somatosensory evoked potentials (SEPs) N20 or P25 waves (42), but they were normal in one patient with pure sensory stroke ( # 8), indicating limited damage to the VPL thalamocortical pathway (43, 44). Finally, recovery from initial metabolic impairment can be one confounding factor (49, but we found no significant relationship between times since onset of stroke and PET data. In the rat, the somatosensory cortex glucose use normalized in less than 2 weeks after the removal of whiskers (46). The apparent lack of metabolic effects in the SM area in our patients must be considered in the light of the clinical impairment, which was prominent in all. Hence, 7/8 patients had some degree of thalamic pain (26,47) including patients # 8 with pure sensory stroke at PET time. Our results suggesting that cortical metabolism is unaltered in patients with thalamic pain agree with Laterre et al. who also found normal cortical metabolism in one patient suffering from “thalamic” pain after a small internal capsular
infarction (48). The hypothesis that hyperactivity of intralaminar thalamic nuclei may be implicated in thalamic pain has been previously formulated (48,50). A role for the cerebral cortex as the main relay of inhibition upon the intralaminar thalamic nuclei remains debated (49); however the lack of prominent cortical hypometabolism in our subjects would support the hypothesis that the loss of intralaminar nuclei inhibition originates at the subcortical, and not at the cortical level. Yet, cortical metabolic activation secondary to hyperactivity of the intralaminar nuclei, if any, could account for the lack of detectable reduction in cortical metabolism. Acknowledgement The authors wish to thank B. Mazoyer MD, PhD, for his helpful advice on statistical analysis.
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