272
Cerebral Hemodynamic Change in the Child and the Adult With Moyamoya Disease Yasuo Kuwabara, MD, Yuichi Ichiya, MD, Makoto Otsuka, MD, Takashi Tahara, MD, Ranjan Gunasekera, MD, Kanehiro Hasuo, MD, Kouji Masuda, MD, Toshio Matsushima, MD, and Masashi Fukui, MD To clarify the differences in cerebral hemodynamics and metabolism between children and adults with bilateral moyamoya disease, we measured regional cerebral blood flow, regional oxygen extraction fraction, regional metabolic rate for oxygen, regional cerebral blood volume, and regional transit time using positron emission tomography in nine patients (five children and four adults) and compared the values with those in controls (four children with unilateral moyamoya disease and six normal adults). The major differences between pediatric and adult patients were in regional cerebral blood volume and regional oxygen extraction fraction. Regional cerebral blood volume was more markedly increased relative to the control value in the children than in the adults. Also, regional oxygen extraction fraction was greater than control in areas with low blood flow in the children but was never increased in the adults. However, in the adults, only regional transit time was significantly prolonged relative to the control values. The increased regional oxygen extraction fraction relative to the control value observed in children with moyamoya disease may explain why transient ischemic attacks are a common symptom in this group. (Stroke 1990;21:272-277)
M
oyamoya disease is well-recognized in Japan and is characterized by stenosis or occlusion of unknown etiology of both internal carotid arteries (ICAs) and of numerous collateral vessels around the circle of Willis.1'2 Peak incidences are among persons aged 0-10 and 30-40 years, and the disease is usually divided into two types, pediatric and adult.23 The types show different clinical courses and features, and the pediatric type is more progressive than the adult type. The common symptoms of moyamoya disease in children are transient ischemic attacks (TTAs) such as hemiparesis or weakness of the limbs, whereas the symptoms in adults are attacks of bleeding such as intracerebral or subarachnoid hemorrhage.3 Many workers have investigated cerebral hemodynamics in patients with moyamoya disease,4-7 but there have been no reports on the differences in cerebral hemodynamics and metabolism between pediatric and adult patients. To our knowledge, we are the first to measure cerebral hemodynamics and From the Department of Radiology, Faculty of Medicine (Y.K., Y.I., M.O., T.T., R.G., K.H., K.M.) and the Department of Neurosurgery, Neurological Institute (T.M., M.F.), Kyushu University, Fukuoka, Japan. Address for correspondence: Yasuo Kuwabara, Department of Radiology, Faculty of Medicine, Kyushu University, Maidashi, Higashi-ku, Fukuoka, 812 Japan. Received February 6, 1989; accepted September 20, 1989.
metabolism and to compare the pediatric with the adult type of moyamoya disease using positron emission tomography (PET). Subjects and Methods
We studied 30 patients with moyamoya disease using PET. The disease was diagnosed in all patients by angiography, which showed stenosis or occlusion of the ICAs and moyamoya vessels on both sides. From these 30 patients, we carefully selected nine (five children and four adults) retrospectively for this study. We excluded patients with multiple cerebral infarcts or recent (^2 months) infarction or hemorrhage to avoid their effects on cerebral blood flow and metabolism. We also excluded adult patients with the onset of moyamoya disease during childhood because they had multiple cerebral infarcts and cerebral atrophy. The clinical features of the nine patients are summarized in Table 1. Five had small low-density lesions on computed tomography (CT). None had a neurologic deficit when the PET study was performed. The PET device (HEADTOME-III, Shimadzu Corp., Kyoto, Japan, and Akita Noken, Akita, Japan) had a transaxial resolution of 8.2 mm and an axial resolution of 13 mm full-width at halfmaximum. Regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), and
Downloaded from http://stroke.ahajournals.org/ by guest on June 24, 2016
Kuwabara el al
Cerebral Hemodynamics and Metabolism in Moyamoya Disease
273
TABLE 1. Clinical Features of Nine Patients and Four Pediatric Controls With Moyamoya Disease Iviajor symptoms
Case/ age/sex
Type
Description
Interval onset-PET
Low-density lesions on CT Location Size (cm2)
Angiographic findings
Pediatric
1/9/F 2/9/M
TIA+IVM
Weakness of R hand Choreic movement
5 months 2 years
3/9/F
TIA
Weakness of L hand
10 months
4/11/F
TIA
Weakness of limbs
TIA
Weakness of L foot
R temporal subcortical None
1x2
5/15/F
4 years 11 months 1 year 4 months
6/33/M 7/35/M
TIA
Weakness of L hand Weakness of L limbs
6 years 6 months
3x3
Headache Headache
4 years 8 years
R frontal cortical L frontal subcortical None R parietal cortical
3 years 1 year 8 months 4 months
8/40/F 9/59/F
TIA
TIA -
Hemorrhage
None R frontal subcortical None
— lxl —
—
1x2 — 2x4
Occlusion Occlusion MCAs Occlusion MCAs Occlusion
of B ICAs of B ACAs and of B ACAs and of B ICAs
Occlusion of B ICAs
Occlusion of B ICAs Stenosis of B ACAs and MCAs Stenosis of B ICAs Occlusion of B ICAs
Pediatric controls
10/8/M 11/9/F
TIA TIA
Weakenss of L hand Paresthesia of R hand
12/9/M
RIND
Weakness of L limbs
13/11/M
TIA
L hemiparesis
2 years 8 months
None None R temporal cortical None
— — 2x2 —
Occlusion of R ICA Occlusion of L ICA Stenosis of R ICA Occlusion of R ICA
PET, positron emission tomography; CT, computed tomography; F, female; M, male; TIA, transient ischemic attack; IVM, involuntary movement; RIND, reversible ischemic neurologic deficit; R, right; L, left; B, bilateral; ICA, internal carotid artery; ACA, anterior cerebral artery; MCA, middle cerebral artery.
regional cerebral metabolic rate for oxygen (rCMRO2) were measured using the oxygen-15 steady-state method8-9 with continuous infusion of H215O or inhalation of C^Oz and 15O2. Regional cerebral blood volume (rCBV) was measured using a single inhalation of "CO or C15O. rOEF and rCMRO2 were corrected for rCBV.9 Regional transit time (rTT) was calculated as rCBV+rCBF.10 A small cannula was placed in the femoral artery for blood sampling. A PET transmission scan with a germanium- 68-gallium- 68 ring source was obtained from each patient for attenuation correction.11 For the oxygen-15 steady-state method, five crosssectional planes 20, 35, 50, 65, and 80 mm above the orbitomeatal line were scanned simultaneously for 6 minutes. Arterial radioactivities were measured every 2 minutes. PaOj, PacOj, and arterial pH were measured at the start and end of each scan and averaged. The values are expressed as mean±SD. The values of rCBF, rOEF, rCMRO2, rCBV, and rTT were obtained using rectangular regions of interest 18x14 or 14x14 mm in the cerebellum, in the frontal, temporal, parietal, and occipital cortices, and in the striatum on both sides (Figure 1) and averaged. The regions of interest were selected from the blood flow images and the CT scan to avoid the low-density lesions shown on CT. The values are expressed as mean±SD.
Age, arterial blood gases, hemoglobin content, rCBF, rOEF, rCMRO2, rCBV, and rTT in the nine patients were compared with those in respective controls (four children with unilateral moyamoya disease [Table 1] and six normal volunteers aged 26-36 years old) using Student's t test and Welch's t test with unequal variance. rCBF, rOEF, rCMRO2, rCBV, and rTT in the angiographically normal hemisphere were used in the pediatric controls. Results Age, arterial blood gases, and hemoglobin content in the pediatric and adult patients with moyamoya disease are compared with values in their respective controls in Table 2. There was no significant difference between the patients and their respective controls. rCBF, rOEF, rCMRO2, rCBV, and rTT in various anatomic regions in the pediatric and adult patients with moyamoya disease are compared with values in their respective controls in Table 3. In the pediatric patients, rCBF was not significantly decreased, although it was approximately 20% lower than control in the frontal and parietal regions; the occipital region and the cerebellum were spared. Adult patients also showed no significant reduction in rCBF, although it was slightly decreased in the entire brain. rCMRO2 was not decreased in the pediatric
Downloaded from http://stroke.ahajournals.org/ by guest on June 24, 2016
274
Stroke
Vol 21, No 2, February 1990
TABLE 2. Age, Arterial Blood Gases, and Hemoglobin Content in Pediatric and Adult Patients With Moyamoya Disease and Respective Controls
Pediatric
Age (yr) PacO} (mm Hg) PaOs (mm Hg) Hemoglobin (g/dl)
Patients ("=5) 10.6+2.6 38.0+3.9 99.0+7.6 13.3+0.9
Adult Controls («=4) 93±1.3 39.7±1.9 89.4±3.9 13.3±0.7
Controls («=6) 29.7±4.3 43.1 ±6.6 88.8±12.0 15.8±0.8
Patients («=4) 41.8±11.9 41.7+4.4 81.9±3.4 14.4±1.9
Values are mean±SD.
TABLE 3. rCBF, rOEF, rCMROj, rCBV, and rTT in Brain Regions of Pediatric and Adult Patients With Moyamoya Disease and Respective Controls
Pediatric
Adult
Patients («=5)
Controls (»=4)
Patients («=4)
Controls ("=6)
rCBF Cerebellum Frontal Temporal Parietal Occipital Striatum
49.0±5.5 35.6±7.8 38.8±15.8 39.6±15.2 37.5±9.6 41.0±6.4
45.9+5.7 45.3+6.7 44.2+5.3 48.4+4.1 35.8+4.5 44.4±7.1
44.4±6.8 31.3+3.0 32.2±3.0 31.0±2.4 29.2±4.7 34.6±3.1
51.0±13.7 37.6+6.1 39.5±8.7 37.9±8.4 32.9±9.3 43.1±11.8
rOEF Cerebellum Frontal Temporal Parietal Occipital Striatum
39.0±5.7 51.3±9.4* 50.2±8.5t 51.7±6.0t 50.6+7.7 47.5 ±6.0
34.9+3.8 34.2±3.5 37.6±4.6 36.7+2.9 42.0±4.3 36.0±3.0
36.1±1.9 39.5±4.4 41.2±3.4 42.5±3.0 41.7±3.3 37.9±2.9
34.8±6.2 37.5±8.7 39.4±7.9 38.8±9.1 42.8±6.9 38.7±10.9
rCMRO2 Cerebellum Frontal Temporal Parietal Occipital Striatum
3.43 ±0.29 3.20+0.60 3.30+0.92 3.56±1.10 3.32±0.67 3.43 ±0.48
2.66±0.28 2.58±0.40 2.78±0.34 3.08±0.45 2.54±0.61 2.64±0.37
2.99±0.39 2.48±0.28 2.54±0.21 2.47±0.16 2.27±0.29 2.45 ±0.19
3.18±0.58 2.84±0.56 2.84±0.33 2.71 ±0.51 2.46±0.32 2.94±0.78
rCBV Cerebellum Frontal Temporal Parietal Occipital Striatum
3.17±0.48 7.63±1.94f 5.88±1.28* 6.33±1.74t 6.98±2.34f 6.46±2.97f
2.61 ±0.18 4.56±1.65 3.48±0.74 3.68±0.57 3.82±1.13 2.77+0.61
2.76±0.29 4.32±0.74 3.99+0.42 3.75+0.63 3.61 ±0.41 3.29±0.50
3.13±0.41 3.79±0.61 3.74±0.55 3.68+0.91 3.75±0.60 2.91 ±0.64
rTT Cerebellum Frontal Temporal Parietal Occipital Striatum
3.87±0.40 13.0±2.60+ 10.5±4.71 10.8±4.25t 11.6±3.84t 9.91±4.73f
3.46±0.55 6.19+2.52 4.79±1.32 4.62±0.% 6.45±1.79 3.72±OJ0
3.77±0.49 8.39±1.78 7.49+0.89t 7.30±1.14t 7.62 ±1.63 5.81 + 1.15
4.02 ±0.86 5.84±0.49 6.02±0.76 5.53±0.86 7.20±0.76 4.89±1.01
Region
rCBF, regional cerebral blood flow as ml/min/100 ml brain; rOEF, regional oxygen extraction fraction as %; rCMROj, regional cerebral metabolic rate for oxygen as ml/min/100 ml brain; rCBV, regional cerebral blood volume as ml/100 ml brain; rTT, regional transit time as seconds. Values are mean±SD. 't|p
Cerebral Hemodynamic Change in the Child and the Adult With Moyamoya Disease Yasuo Kuwabara, MD, Yuichi Ichiya, MD, Makoto Otsuka, MD, Takashi Tahara, MD, Ranjan Gunasekera, MD, Kanehiro Hasuo, MD, Kouji Masuda, MD, Toshio Matsushima, MD, and Masashi Fukui, MD To clarify the differences in cerebral hemodynamics and metabolism between children and adults with bilateral moyamoya disease, we measured regional cerebral blood flow, regional oxygen extraction fraction, regional metabolic rate for oxygen, regional cerebral blood volume, and regional transit time using positron emission tomography in nine patients (five children and four adults) and compared the values with those in controls (four children with unilateral moyamoya disease and six normal adults). The major differences between pediatric and adult patients were in regional cerebral blood volume and regional oxygen extraction fraction. Regional cerebral blood volume was more markedly increased relative to the control value in the children than in the adults. Also, regional oxygen extraction fraction was greater than control in areas with low blood flow in the children but was never increased in the adults. However, in the adults, only regional transit time was significantly prolonged relative to the control values. The increased regional oxygen extraction fraction relative to the control value observed in children with moyamoya disease may explain why transient ischemic attacks are a common symptom in this group. (Stroke 1990;21:272-277)
M
oyamoya disease is well-recognized in Japan and is characterized by stenosis or occlusion of unknown etiology of both internal carotid arteries (ICAs) and of numerous collateral vessels around the circle of Willis.1'2 Peak incidences are among persons aged 0-10 and 30-40 years, and the disease is usually divided into two types, pediatric and adult.23 The types show different clinical courses and features, and the pediatric type is more progressive than the adult type. The common symptoms of moyamoya disease in children are transient ischemic attacks (TTAs) such as hemiparesis or weakness of the limbs, whereas the symptoms in adults are attacks of bleeding such as intracerebral or subarachnoid hemorrhage.3 Many workers have investigated cerebral hemodynamics in patients with moyamoya disease,4-7 but there have been no reports on the differences in cerebral hemodynamics and metabolism between pediatric and adult patients. To our knowledge, we are the first to measure cerebral hemodynamics and From the Department of Radiology, Faculty of Medicine (Y.K., Y.I., M.O., T.T., R.G., K.H., K.M.) and the Department of Neurosurgery, Neurological Institute (T.M., M.F.), Kyushu University, Fukuoka, Japan. Address for correspondence: Yasuo Kuwabara, Department of Radiology, Faculty of Medicine, Kyushu University, Maidashi, Higashi-ku, Fukuoka, 812 Japan. Received February 6, 1989; accepted September 20, 1989.
metabolism and to compare the pediatric with the adult type of moyamoya disease using positron emission tomography (PET). Subjects and Methods
We studied 30 patients with moyamoya disease using PET. The disease was diagnosed in all patients by angiography, which showed stenosis or occlusion of the ICAs and moyamoya vessels on both sides. From these 30 patients, we carefully selected nine (five children and four adults) retrospectively for this study. We excluded patients with multiple cerebral infarcts or recent (^2 months) infarction or hemorrhage to avoid their effects on cerebral blood flow and metabolism. We also excluded adult patients with the onset of moyamoya disease during childhood because they had multiple cerebral infarcts and cerebral atrophy. The clinical features of the nine patients are summarized in Table 1. Five had small low-density lesions on computed tomography (CT). None had a neurologic deficit when the PET study was performed. The PET device (HEADTOME-III, Shimadzu Corp., Kyoto, Japan, and Akita Noken, Akita, Japan) had a transaxial resolution of 8.2 mm and an axial resolution of 13 mm full-width at halfmaximum. Regional cerebral blood flow (rCBF), regional oxygen extraction fraction (rOEF), and
Downloaded from http://stroke.ahajournals.org/ by guest on June 24, 2016
Kuwabara el al
Cerebral Hemodynamics and Metabolism in Moyamoya Disease
273
TABLE 1. Clinical Features of Nine Patients and Four Pediatric Controls With Moyamoya Disease Iviajor symptoms
Case/ age/sex
Type
Description
Interval onset-PET
Low-density lesions on CT Location Size (cm2)
Angiographic findings
Pediatric
1/9/F 2/9/M
TIA+IVM
Weakness of R hand Choreic movement
5 months 2 years
3/9/F
TIA
Weakness of L hand
10 months
4/11/F
TIA
Weakness of limbs
TIA
Weakness of L foot
R temporal subcortical None
1x2
5/15/F
4 years 11 months 1 year 4 months
6/33/M 7/35/M
TIA
Weakness of L hand Weakness of L limbs
6 years 6 months
3x3
Headache Headache
4 years 8 years
R frontal cortical L frontal subcortical None R parietal cortical
3 years 1 year 8 months 4 months
8/40/F 9/59/F
TIA
TIA -
Hemorrhage
None R frontal subcortical None
— lxl —
—
1x2 — 2x4
Occlusion Occlusion MCAs Occlusion MCAs Occlusion
of B ICAs of B ACAs and of B ACAs and of B ICAs
Occlusion of B ICAs
Occlusion of B ICAs Stenosis of B ACAs and MCAs Stenosis of B ICAs Occlusion of B ICAs
Pediatric controls
10/8/M 11/9/F
TIA TIA
Weakenss of L hand Paresthesia of R hand
12/9/M
RIND
Weakness of L limbs
13/11/M
TIA
L hemiparesis
2 years 8 months
None None R temporal cortical None
— — 2x2 —
Occlusion of R ICA Occlusion of L ICA Stenosis of R ICA Occlusion of R ICA
PET, positron emission tomography; CT, computed tomography; F, female; M, male; TIA, transient ischemic attack; IVM, involuntary movement; RIND, reversible ischemic neurologic deficit; R, right; L, left; B, bilateral; ICA, internal carotid artery; ACA, anterior cerebral artery; MCA, middle cerebral artery.
regional cerebral metabolic rate for oxygen (rCMRO2) were measured using the oxygen-15 steady-state method8-9 with continuous infusion of H215O or inhalation of C^Oz and 15O2. Regional cerebral blood volume (rCBV) was measured using a single inhalation of "CO or C15O. rOEF and rCMRO2 were corrected for rCBV.9 Regional transit time (rTT) was calculated as rCBV+rCBF.10 A small cannula was placed in the femoral artery for blood sampling. A PET transmission scan with a germanium- 68-gallium- 68 ring source was obtained from each patient for attenuation correction.11 For the oxygen-15 steady-state method, five crosssectional planes 20, 35, 50, 65, and 80 mm above the orbitomeatal line were scanned simultaneously for 6 minutes. Arterial radioactivities were measured every 2 minutes. PaOj, PacOj, and arterial pH were measured at the start and end of each scan and averaged. The values are expressed as mean±SD. The values of rCBF, rOEF, rCMRO2, rCBV, and rTT were obtained using rectangular regions of interest 18x14 or 14x14 mm in the cerebellum, in the frontal, temporal, parietal, and occipital cortices, and in the striatum on both sides (Figure 1) and averaged. The regions of interest were selected from the blood flow images and the CT scan to avoid the low-density lesions shown on CT. The values are expressed as mean±SD.
Age, arterial blood gases, hemoglobin content, rCBF, rOEF, rCMRO2, rCBV, and rTT in the nine patients were compared with those in respective controls (four children with unilateral moyamoya disease [Table 1] and six normal volunteers aged 26-36 years old) using Student's t test and Welch's t test with unequal variance. rCBF, rOEF, rCMRO2, rCBV, and rTT in the angiographically normal hemisphere were used in the pediatric controls. Results Age, arterial blood gases, and hemoglobin content in the pediatric and adult patients with moyamoya disease are compared with values in their respective controls in Table 2. There was no significant difference between the patients and their respective controls. rCBF, rOEF, rCMRO2, rCBV, and rTT in various anatomic regions in the pediatric and adult patients with moyamoya disease are compared with values in their respective controls in Table 3. In the pediatric patients, rCBF was not significantly decreased, although it was approximately 20% lower than control in the frontal and parietal regions; the occipital region and the cerebellum were spared. Adult patients also showed no significant reduction in rCBF, although it was slightly decreased in the entire brain. rCMRO2 was not decreased in the pediatric
Downloaded from http://stroke.ahajournals.org/ by guest on June 24, 2016
274
Stroke
Vol 21, No 2, February 1990
TABLE 2. Age, Arterial Blood Gases, and Hemoglobin Content in Pediatric and Adult Patients With Moyamoya Disease and Respective Controls
Pediatric
Age (yr) PacO} (mm Hg) PaOs (mm Hg) Hemoglobin (g/dl)
Patients ("=5) 10.6+2.6 38.0+3.9 99.0+7.6 13.3+0.9
Adult Controls («=4) 93±1.3 39.7±1.9 89.4±3.9 13.3±0.7
Controls («=6) 29.7±4.3 43.1 ±6.6 88.8±12.0 15.8±0.8
Patients («=4) 41.8±11.9 41.7+4.4 81.9±3.4 14.4±1.9
Values are mean±SD.
TABLE 3. rCBF, rOEF, rCMROj, rCBV, and rTT in Brain Regions of Pediatric and Adult Patients With Moyamoya Disease and Respective Controls
Pediatric
Adult
Patients («=5)
Controls (»=4)
Patients («=4)
Controls ("=6)
rCBF Cerebellum Frontal Temporal Parietal Occipital Striatum
49.0±5.5 35.6±7.8 38.8±15.8 39.6±15.2 37.5±9.6 41.0±6.4
45.9+5.7 45.3+6.7 44.2+5.3 48.4+4.1 35.8+4.5 44.4±7.1
44.4±6.8 31.3+3.0 32.2±3.0 31.0±2.4 29.2±4.7 34.6±3.1
51.0±13.7 37.6+6.1 39.5±8.7 37.9±8.4 32.9±9.3 43.1±11.8
rOEF Cerebellum Frontal Temporal Parietal Occipital Striatum
39.0±5.7 51.3±9.4* 50.2±8.5t 51.7±6.0t 50.6+7.7 47.5 ±6.0
34.9+3.8 34.2±3.5 37.6±4.6 36.7+2.9 42.0±4.3 36.0±3.0
36.1±1.9 39.5±4.4 41.2±3.4 42.5±3.0 41.7±3.3 37.9±2.9
34.8±6.2 37.5±8.7 39.4±7.9 38.8±9.1 42.8±6.9 38.7±10.9
rCMRO2 Cerebellum Frontal Temporal Parietal Occipital Striatum
3.43 ±0.29 3.20+0.60 3.30+0.92 3.56±1.10 3.32±0.67 3.43 ±0.48
2.66±0.28 2.58±0.40 2.78±0.34 3.08±0.45 2.54±0.61 2.64±0.37
2.99±0.39 2.48±0.28 2.54±0.21 2.47±0.16 2.27±0.29 2.45 ±0.19
3.18±0.58 2.84±0.56 2.84±0.33 2.71 ±0.51 2.46±0.32 2.94±0.78
rCBV Cerebellum Frontal Temporal Parietal Occipital Striatum
3.17±0.48 7.63±1.94f 5.88±1.28* 6.33±1.74t 6.98±2.34f 6.46±2.97f
2.61 ±0.18 4.56±1.65 3.48±0.74 3.68±0.57 3.82±1.13 2.77+0.61
2.76±0.29 4.32±0.74 3.99+0.42 3.75+0.63 3.61 ±0.41 3.29±0.50
3.13±0.41 3.79±0.61 3.74±0.55 3.68+0.91 3.75±0.60 2.91 ±0.64
rTT Cerebellum Frontal Temporal Parietal Occipital Striatum
3.87±0.40 13.0±2.60+ 10.5±4.71 10.8±4.25t 11.6±3.84t 9.91±4.73f
3.46±0.55 6.19+2.52 4.79±1.32 4.62±0.% 6.45±1.79 3.72±OJ0
3.77±0.49 8.39±1.78 7.49+0.89t 7.30±1.14t 7.62 ±1.63 5.81 + 1.15
4.02 ±0.86 5.84±0.49 6.02±0.76 5.53±0.86 7.20±0.76 4.89±1.01
Region
rCBF, regional cerebral blood flow as ml/min/100 ml brain; rOEF, regional oxygen extraction fraction as %; rCMROj, regional cerebral metabolic rate for oxygen as ml/min/100 ml brain; rCBV, regional cerebral blood volume as ml/100 ml brain; rTT, regional transit time as seconds. Values are mean±SD. 't|p
