:Acta
Acta Neurochir (Wien) (1990) 105:107-111
.
uroch rurgica
9 by Springer-Verlag 1990
Cerebral Blood Flow in Moyamoya Disease Part 2: Autoregulation and COz Response A. Ogawa, N. Nakamura, T. Yoshimoto, and J. Suzuki Division of Neurosurgery, Institute of Brain Diseases, Tohoku University School of Medicine, Seiryo-machi, Sendal, Japan
Summary In order to clarify the cerebrovascular response in Moyamoya disease, the autoregulation and C Q response was investigated using the 8~mKr continuous cerebral blood flow (CBF) measurement technique. A total of 32 measurements were made over the anterior and posterior circulation in 16 Moyamoya patients (seven adults, nine children). CBF measurements were made during four loading trials (hypertension, hypotension, CO 2 inhalation and hyperventilation). Study was then made of the vascular response of the frontal lobe, perfused by the internal carotid artery (ICA), and the occipital lobe and cerebellum, perfused by the vertebral artery (VA). Deficits of autoregulation were more severe among the juvenile cases in response to hypotension than to hypertension in both the ICA and VA regions, but the deficits were mild. The CO2 response to hypercapnea in the juvenile cases tended to be abnormal in both the ICA and VA regions. Both adult and juvenile patients showed deficits in the ICA region in response to hyperventilation, some of whom exhibited paradoxial responses. Notable differences in the severity of the deficits of the vascular response in adult and juvenile cases were seen, with the deficits in the response being more severe among the juvenile cases. Moreover, significant regional differences in the deficits were also found.
Keywords." Cerebral blood flow; moyamoya disease; autoregulation C Q response.
Introduction T h e a b n o r m a l v a s c u l a r n e t w o r k seen in M o y a m o y a disease is n o w k n o w n to be c o l l a t e r a l p a t h w a y s dev e l o p i n g d u e to t h e g r a d u a l o c c l u s i o n o f u n k n o w n aet i o l o g y o f the b o t h i n t e r n a l c a r o t i d a r t e r i e s 22-25. I n spite o f the f a c t t h a t the d i s e a s e is f u n d a m e n t a l l y a n o c c l u s i v e d i s o r d e r , r e l a t i v e l y few studies h a v e b e e n r e p o r t e d c o n c e r n i n g t h e c e r e b r a l b l o o d f l o w in s u c h p a t i e n t s . W e h a v e p r e v i o u s l y r e p o r t e d t h a t t h e r e a r e d e c r e a s e s in the h e m i s p h e r i c b l o o d flow, p a r t i c u l a r l y a m o n g y o u n g e r patients, that the pattern of regional cerebral blood f l o w ( r C B F ) d o e s n o t s h o w the f r o n t a l d o m i n a n c e c h a r -
acteristic o f n o r m a l subjects, b u t r a t h e r a n o c c i p i t a l dominance12,15,16 T h e r e h a v e b e e n a l m o s t n o r e p o r t s o n the v a s c u l a r r e s p o n s e o f c e r e b r a l vessels in M o y a m o y a
disease. I n
t h e p r e s e n t s t u d y we h a v e e x a m i n e d the c e r e b r a l b l o o d f l o w in t h e r e g i o n s p e r f u s e d b y t h e i n t e r n a l c a r o t i d a r t e r y ( I C A ) a n d t h a t p e r f u s e d by t h e v e r t e b r a l a r t e r y ( V A ) u s i n g a n 81 m K r c o n t i n u o u s i n f u s i o n t e c h n i q u e 13,14 a n d h a v e s t u d i e d the a u t o r e g u l a t i o n a n d CO2 r e s p o n s e s o f t h e vessels in these r e g i o n s .
Clinical Materials and Methods Patients included are nine children and seven adults with Moyamoya disease. Five of the children were female and four were male, and ages ranged from 6 to 14 years. Except for one case in which onset was intraventricular haemorrhage, all had experienced transient ischaemic attacks. Among the adult patients, there were four females and three males, and ages ranged from 28 to 48 years. Onset in the adult cases was intraventricular haemorrhage in three cases, transient ischaemic attacks in three cases, and one asymptomatic case. In all cases, neurological symptoms were absent or mild at the time of CBF measurement. Cerebral blood flow was measured at two locations in each case, one in the region of perfusion of the ICA and one in the region of perfusion of the VA. Measurements were made after at least two months from onset and recordings from the ICA region were made at an interval of 1-2 weeks before or after those from the VA. The procedure was as follows: A catheter was led from the femoral artery and selectively placed in the ICA and VA. Following angiography, CBF measurements were made in the awake state. The blood flow measurements were made using the 81mKr continuous measurements technique TM14 81mKr extracted by passage of 5% glucose in Rb-Kr generator (Nihon Mediphysics), was continuously infused and radio activity was recorded at 10 sec intervals over the skull and cervical region using a gamma camera (Toshiba GCA 301) placed in prallel with the sagittal plane. Data analysis was done using a Toshiba GMS-80 A Data Processor. After the CBF was measured during rest, the vascular response was tested. Blood pressure was raised, then lowered, followed by
108
A. Ogawa etal.: Cerebral Blood Flow in Moyamoya Disease
C O 2 inhalation and hyperventilation. Hypertension was induced by venous drip of Angiotensin II for five minutes, causing an increase in blood pressure of 30-40 mmHg. Hypotension was induced by a venous drip of Trimethaphan, resulting in a decrease of 15~0 mmHg for about six minutes. Hypercapnea was produced by inhalation of 5% CO2 gas for four minutes. Hyperventilation was induced by instructing the patient to breath deeply for four minutes. During this entire period, blood pressure and blood gases were continuously monitored. In the analysis of the vascular response, study was made of the region of interest in the frontal lobe for the anterior circulation and in the occipital lobe and cerebellar hemisphere for the posterior circulation.In the autoregulation study, an autoregulation index (A % CBF/A BP) was calculated as the changes in blood flow during loading as compared to those during rest, while eliminating the effects of blood pressure changes. Similarly, in the study of the CO2 response, a CO2 response index ( • % CBF/& PaCO2) was calculated as the changes in blood flow, while eliminating the effects of PaCO2 change. For the evaluation of the results, those measurements in which sufficient changes in the blood pressure of PaCO2 were not obtained were excluded from the analysis.
A%CB%BP
Frontal lobe ~_ Occipital lobe Cerebellum
0
i ii
9
o
9
o
n=4 n--=-7 n=7
n=4 n=5 n=5
Child group
Adult group
Fig. 2. Autoregulation in response to hypotension
Results
l. Autoregulation in Response to Hypertension (Fig. 1) The autoregulation index scores in the frontal lobe, occipital lobe and cerebellum of the juvenile cases were 0.6 4- 0.59, 0.16 4- 0.27 and 0.26 4- 0.38, respectively. Although autoregulation was fairly well maintained in the cerebellum and occipital lobe, which are perfused by the VA, mild deficits of autoregulation were apparent in the frontal lobe, which is perfused by the ICA. In the adult cases, the autoregulation index scores were 0.74- 1.3, 0.094- 0.23 and 0.09 4- 0.23 in, respectively, the frontal lobe, occipital lobe and cerebellum. Similar to the juvenile cases, autoregulation was generally preserved in the cerebellum and occipital lobe,
Frontal lobe
A%CBF/~PaCO, Occipital lobe Cerebellum
6]
~
4-
" I
ol
20
0
!l"
col m
-2-
n=4
n=5
n=5
Child group
Adult group
Frontal lobe Occipital lobe Cerebellum
1
"
--2"
n=7 n=7
Child group
perfused by the VA, but mild deficits were apparent in regions perfused by the ICA.
2. Autoregulation in Response to Hypotension (Fig. 2)
i
--1"
n=7
n=4
Fig. 3, CO2 response to hypocapnea by CO2 inhalation
A%CB~'~B p
i
n=5 n=4
n=6
n=7 n=7
Adult group
Fig. 1. Autoregulation in response to hypertension
The autoregulation index scores among the juvenile cases were - 0.8 + 0.73, - 0.76 4- 0.77 and - 0.87 4- l. 17 in the frontal lobe, occipital lobe and cerebellum, respectively. Autoregulation was disrupted at all of these sites. In the adult cases, the autoregulation index scores of the frontal lobe, occipital lobe and cerebellum were, respectively, - 0.08 + 1.68, - 0.32 4- 0.72, - 0.22 4- 0.35. Unlike the autoregulation in response to hypotension
A. Ogawa etal.: Cerebral Blood Flow in Moyamoya Disease
~%CBF/ /APaCO~ o
8-
Frontal
lobe
6-
Occipital lobe
4-
Cerebellum
20
-2. --
i
and cerebellum, perfused by the VA, was relatively favourable. Among the adult cases, these scores were - 1.22 4- 2.82, - 3.26 4- 0.7 and - 3.11 4- 1.03 for the frontal lobe, occipital lobe, and cerebellum, respectively. Three of the seven patients showed deficits in the frontal lobe, two of which were paradoxical responses. Normal responses were recorded from the occipital lobe and cerebellum.
Discussion
4-
o -6 --
109
m
8-
-10 -12-
.-
n=5 n=3 n=3
n=7 n=7 n=7
Child group
Adult group
Fig. 4. CO2 response to hypocapnea by hypoventi|ation
in the juvenile cases, that in the adult cases was relatively preserved.
3. The C02 Response to Hypercapnea (Fig. 3) The CO2 response index scores of the fronatl lobe, occipital lobe and cerebellum among the juvenile cases were, respectively, 2.4 + 3.06, 3.14 + 4.34, 1.8 i 2.46. Individually, two of four patients showed disappearance of the CO2 response in the frontal lobe, two of five in the occipital lobe, and three of five in the cerebellum. Among the adults, the CO2 response index scores were 2.86+1.79. 2.684-0.39 and 3.234-0.98 for the frontal lobe, occipital lobe and cerebellum, respectively. Individually, only one patient showed deficits of the CO2 response in the frontal lobe, indicating a considerably better situation than that found among the juvenile cases.
4. The C02 Response to Hyperventilation (Fig. 4) Among the juvenile cases, the CO2 response index scores were -0.984-6.14, -6.034-6.33 and - 5.88 + 6.47, respectively, in the frontal lobe, occipital lobe, and cerebellum. Two of the five patients showed deficits in the frontal lobe, one of which showed a paradoxical response. The response in the occipital lobe
The first study on the cerebral haemodynamics of Moyamoya disease was that of Takahashi et aL 27. In 1967, in which a NzO technique was used to measure the blood flow of the entire brain in six patients. Since then, various techniques have been used, including Xearterial infusion 9'28, Xe-venous infusion ~2'15, Argoninhalation 6, and recently three-dimensional PET scan 4. Debate has continued whether or not a reduction in cerebral blood flow occurs Moyamoya patients, but recently some consensus has been reached that, in comparison with normal children, there is a reduction in cerebral blood flow in juvenile Moyamoya cases. However, there have been no previous reports of the vascular response in this disorder and many uncertainties remain with regard to the underlying pathophysiology. We have previously reported details concerning our technique for making continuous measurements of changes in regional cerebral blood flow 12'16. In the present study, we have clarified certain aspects of the vascular response found in Moyamoya disease using this method. This method anables one to monitor serial changes in cerbral blood flow. By applying loads during such monitoring, it is possible to measure the changes in blood flow caused by specific conditions. For this reason, this method is particulary suitable for making measurements of the vascular response. It was found that the autoregulation in induced hypertension was relatively well-maintained in our patients. The autoregutation in the region of perfusion of the VA was especially well maintained, whereas deficits in the region of the ICA were not infrequent. In contrast, deficits in the response to hypotension were more often found than that to hypertension in both the regions of perfusion of the ICA and that of the VA. Particularly notable was the difference between the adult and juvenile Moyamoya cases in the autoregulation response to hypertension-the juvenile cases showing much stronger deficits. Nevertheless, usage of
110
the same technique for measuring autoregulation in other diseases has produced Autoregulation Index values in excess of 4-2.0, indicating that the deficits of autoregulation in both adult and juvenile Moyamoya disease are relatively mild. With regard to the CO2 Response Index, others have previously reported that normal subjects show values in excess of 1.0 and ranging between 2 and 42, 19,21. In the present study, we have found that a normal CO2 response to hypercapnea was maintained among the adult cases in both the region of the ICA and that of the VA. Abnormalities were found, however, in more than half of the juvenile cases. In response to hyperventilation, all of the adult cases showed normal responses in the region of the VA, whereas cases of paradoxical responses were seen among both the adult and juvenile cases in the region of the ICA. Moreover, among the juvenile cases there were also cases in which strong responses were seen both in the region of the VA and that of the ICA. In summary, there were mild but clear deficits in the autoregulation in response to hypotension and CO2 response to hypercapnea which, during the regulation of cerebral dynamics, require dilatation of blood vessels. These findings indicate that the regulated vessels, which control to vascular response, are in a state in which they cannot be dilatated. In a comparison of the autoregulation found in the adult and juvenile cases, it was seen that, despite the fact that the angiographic stage of the Moyamoya disease was more advanced in the adult cases, the deficits in the vascular responsiveness of the juvenile cases were greater. This difference is thought to be due to an intrinsic difference in the nature of adult and juvenile Moyamoya disease. That is, unlike adult Moyamoya disease, the onset in children usually involves ischaemic symptoms3,10,11,18 and there is normally a progression ot the vascular occlusive lesion in follow-up angiograms23'24'26. Moreover, there are conspicuous differences in the clinical picture of adult and juvenile Moyamoya disease25, such as the notable decrease in cerebral blood flow among the juvenile cases 12. The progression in the vascular occlusive lesion and the marked reduction in blood flow in comparison with normals suggests that the brain of the child with Moyamoya disease is in a continually ischaemic state. This conclusion is thought to be supported by the fact that, although relatively mild, the deficits of vascular responsiveness in juvenile cases are more severe than those in adult cases. It was also found that the deficits of responsiveness
A. Ogawa etal.: Cerebral Blood Flow in Moyamoya Disease
were more severe in the region of perfusion of the ICA than that of the VA. It is of course well-known that Moyamoya disease is a progressive, occlusive disorder of the ICA and that, in cerebral angiograms, blood supply is achieved through non-physiological pathways, such as through the medullary artery via the basal Moyamoya vessels, through the ethmoidal Moyamoya vessels via the ophthalmic artery or through the Vault Moyamoya vessels via the external carotid artery7. It is therfore thought likely that stronger deficits will arise in the region perfused by the ICA than that perfused by the VA. EEG studies in cases of juvenile Moyamoya disease have demonstrated the so-called "re-build up" phenomenon following hyperventilation1. All of the juvenile cases of the present study also showed such rebuild up. EEG redordings were not in fact taken during the haemodynamic measurements, but a tendency was found for a marked reduction in blood flow, particularly in the region of the VA. Within 5-10 minutes of the completion of hyperventilation, however, full recovery of cerbraI haemodynamics was seen. Moreover, in light of the fact that there were several cases which showed an increase in blood flow during and immediately after the hyperventilation in the region of the ICA, it is evident that the re-build up seen after hyperventilation cannot be explained solely as a reduction in blood flow. In fact, it has been reported that there is a suppression of breathing following hyperventilation, during which a decrease in the arterial PaO2 is observed 17, and that, following hyperventilation in juvenile Moyamoya cases, there is a decrease in oxygen consumption4. In the light of the above findings, we conclude that the vascular responses in Moyamoya disease are notably different both in adult and juvenile cases, and in the region of perfusion of the ICA and that of the VA. A variety of surgical treatment for Moyamoya disease, such as superior cervical ganglionectomy2~ 22 and vascular reconstruction5'8, have been reported, but their proper evaluation requires detailed study of the vascular responses following treatment.
References
1. KodamaN, AokiY, HiragaH, WadaT, Suzuki J (1979) Electroencephalographic findingsin children with moyamoyadisease. Arch Neurol 36:16-19 2. Iliff LD, Zilkha E, Du BoulayGH, MarshallJ, Russel RWR, SymonL (1974) CerebrovascularCO2reactivityof the fast and slow clearingcompartments.Stroke 5:607-611
A. Ogawa et al.: Cerebral Blood Flow in Moyamoya Disease 3. Isono M, Yonemitsu T, Fujiwara S, Kodama N, Suzuki J (1981) Epidemiological study on moyamoya disease: From the experiences of 100 cases. In: Proceeding of the 10th Japanese conference on surgery of cerebral stroke. Neuron, Tokyo, pp 3-7 4. Kameyama M, Shirane R, Tsurumi Y, Fujiwara S, Takahashi A, Suzuki J, Ito M, Ido T (1986) Cerebral blood flow and metabolism in childhood Moyamoya disease. An investigation into "re-build-up" phenomenon on EEG by positron CT, Child's Nerv Syst 2:130-133 5. Karasawa J, Kikuchi H, Furuse S, Kawamura J, Sasaki T (1978) Treatment of moyamoya disease with S T A - MCA anastomosis. J Neurosurg 49:679-688 6. Karasawa J, Kikuchi H, Kuriyama Y, Sawa T, Kuro M, Kobayashi K, Koike T, Mitsugi T (1981) Cerebral hemodynamics in "Moyamoya" disease. II. Measurements of cerebral circulation and metabolism by use of the argon desaturation method in pre- and post- neurosurgical procedures. Nenrol Med Chir (Tokyo) 21:1161 1168 7. Kodama N, Fujiwara S, Horie Y, Kayama T, Suzuki J (1980) Transdurai anastromosis in moyamoya disease: vault moyamoya. Neurol Surg (Tokyo) 8:729-737 8. Matsushima Y, Fukai N, Tanaka K, Tsuruoka S, Aoyagi M, Ohno K (1981) A new surgical treatment of moyamoya disease in children. A preliminary report. Surg Neurol 15:313-320 9. Nishimoto A, Ueta K, Kuyama H, Takemoto M, Arimitsu T, Mizukawa N (1976) Cerebral hemodynamics in moyamoya disease. In: Reports by the research committee on spontaneous occlusion of the circle of Willis. Japanese Ministry of Health and Welfare, Tokyo, pp 76-82 10. Nishimoto A, Takeuchi S (1967) Cerebral basal rete mirabile. In: Kudo T (ed) A disease with abnormal intracranial vascular networks. Spontaneous occlusion of the circle of Willis. Igaku shoin, Tokyo, pp 56-59 [in Japanese] I1. Nishimoto A (1979) Moyamoya disease. Neurol Med Chir (Tokyo) 19:221-228 12. Ogawa A, Kogure T, Fujiwara S, Kodama N, Suzuki J, Sakurai Y, Wada N (1981) Regional cerebral blood flow on moyamoya disease: study with 133Xe intravenous injection method. In: Proceeding of the 10th Japanese conference on surgery of cerebral stroke. Neuron, Tokyo, pp 189-194 13. Ogawa A, Sakurai Y, Suzuki J (1981) Continuous measurement of regional cerebral blood flow using 81mkrypton ' A preliminary report. Jpn J Nucl Med 18:329 331 !4. Ogawa A, Sakurai Y, Suzuki J (1983) Continuous measurement of regional cerebral blood flow using krypton-81 m. Stroke 14: 623427
111 15. Ogawa A, Sakurai Y, Kayama T, Yoshimoto T (1989) Regional cerebral blood flow with age: changes in rCBF in chiIdhood. Neurol Res. 11:173-176 16. Ogawa A, Yoshimoto T Suzuki T, Sakurai J (1990) Cerebral blood flow in moyamoya disease. Part 1: Correlation with age and regional distribution, Acta Neurochir. (Wien) 105:30-34 17. Ohyama H, Niizuma H, Fujiwara H, Suzuki J (1985) EEG findings in moyamoya disease in children-Concerning with causal genesis of re-build up. Neurol Surg 13:727-733 18. Ozawa E, Taneda M, Kataoka K, Ozaki K, Kaneda H, Irino T (1981) Moyamoya disease admitted as stroke. 10th Japanese Conference on Surgery for Cerebral Stroke: 217-220 19. Reivich M (1964) Arterial PCOz and cerebral hemodynamics. Am J Physiol 206:25-35 20. Sato S, Suzuki J (1975) Anatomical mapping of the cerebral nerve vasorum in the human brain. J. Neurosurg 13:559-568 21. Seki H, Yoshimoto T, Ogawa A, Suzuki J (1984) The CO 2 response in focal cerebral ischemia- Sequential changes following recirculation. Stroke 15:699 704 22. Suzuki J, Takaku A, Kodama N, Sato S (1975) An attempt to treat cerebrovascular "Moyamoya" disease in children. Child's Brain 1:193-206 23. Suzuki J, Kowada M, Asahi M, Takaku A (1965) Diseases showing the "fibrille" like vessels at the base of brain. Frequently found in Japan. Brain Nerve (Tokyo) 17:767-776 24. Suzuki J, Takaku A, Asahi M (1966) The disease showing the abnormal vascular network at the base of brain, particularly found in Japan. II. A follow-up study. Brain Nerve (Tokyo) 18: 897-908 25. Suzuki J, Takaku A (1969)Cerebrovascular moyamoya disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 20:288-299 26. Takahashi A, Fujiwara S, Suzuki J (1985) Cerebral angiography following hyperventilation on moyamoya disease - In reference to "re-build up" phenomenon on EEG. Neurol Surg 13:255-264 27. Takahashi S, Kutsuzawa T, Takahashi S (1967) Studies on cerebral hemodynamics. In: Kudo T (ed) A disease with abnormal intracranial vascular networks. Spontaneous occlusion of the circle of Willis. Igaku shoin, Tokyo, pp 35-37 28. Uemura K, Yamaguchi K, Kojima S, Sakurai Y, Ito Z, Kawakami H, Kutsuzawa T (1975) Regional cerebral blood flow on cerebrovascular "moyamoya" disease: Study by 133Xe clearance method and cerebral angiography. Brain Nerve (Tokyo) 27:385-393 Correspondence and Reprints: Akira Ogawa, M.D., Division of Neurosurgery, Institute of Brain Diseases, Tohoku University, School of Medicine, 1-1 Seiryomachi, Sendai 980, Japan.
Acta Neurochir (Wien) (1990) 105:107-111
.
uroch rurgica
9 by Springer-Verlag 1990
Cerebral Blood Flow in Moyamoya Disease Part 2: Autoregulation and COz Response A. Ogawa, N. Nakamura, T. Yoshimoto, and J. Suzuki Division of Neurosurgery, Institute of Brain Diseases, Tohoku University School of Medicine, Seiryo-machi, Sendal, Japan
Summary In order to clarify the cerebrovascular response in Moyamoya disease, the autoregulation and C Q response was investigated using the 8~mKr continuous cerebral blood flow (CBF) measurement technique. A total of 32 measurements were made over the anterior and posterior circulation in 16 Moyamoya patients (seven adults, nine children). CBF measurements were made during four loading trials (hypertension, hypotension, CO 2 inhalation and hyperventilation). Study was then made of the vascular response of the frontal lobe, perfused by the internal carotid artery (ICA), and the occipital lobe and cerebellum, perfused by the vertebral artery (VA). Deficits of autoregulation were more severe among the juvenile cases in response to hypotension than to hypertension in both the ICA and VA regions, but the deficits were mild. The CO2 response to hypercapnea in the juvenile cases tended to be abnormal in both the ICA and VA regions. Both adult and juvenile patients showed deficits in the ICA region in response to hyperventilation, some of whom exhibited paradoxial responses. Notable differences in the severity of the deficits of the vascular response in adult and juvenile cases were seen, with the deficits in the response being more severe among the juvenile cases. Moreover, significant regional differences in the deficits were also found.
Keywords." Cerebral blood flow; moyamoya disease; autoregulation C Q response.
Introduction T h e a b n o r m a l v a s c u l a r n e t w o r k seen in M o y a m o y a disease is n o w k n o w n to be c o l l a t e r a l p a t h w a y s dev e l o p i n g d u e to t h e g r a d u a l o c c l u s i o n o f u n k n o w n aet i o l o g y o f the b o t h i n t e r n a l c a r o t i d a r t e r i e s 22-25. I n spite o f the f a c t t h a t the d i s e a s e is f u n d a m e n t a l l y a n o c c l u s i v e d i s o r d e r , r e l a t i v e l y few studies h a v e b e e n r e p o r t e d c o n c e r n i n g t h e c e r e b r a l b l o o d f l o w in s u c h p a t i e n t s . W e h a v e p r e v i o u s l y r e p o r t e d t h a t t h e r e a r e d e c r e a s e s in the h e m i s p h e r i c b l o o d flow, p a r t i c u l a r l y a m o n g y o u n g e r patients, that the pattern of regional cerebral blood f l o w ( r C B F ) d o e s n o t s h o w the f r o n t a l d o m i n a n c e c h a r -
acteristic o f n o r m a l subjects, b u t r a t h e r a n o c c i p i t a l dominance12,15,16 T h e r e h a v e b e e n a l m o s t n o r e p o r t s o n the v a s c u l a r r e s p o n s e o f c e r e b r a l vessels in M o y a m o y a
disease. I n
t h e p r e s e n t s t u d y we h a v e e x a m i n e d the c e r e b r a l b l o o d f l o w in t h e r e g i o n s p e r f u s e d b y t h e i n t e r n a l c a r o t i d a r t e r y ( I C A ) a n d t h a t p e r f u s e d by t h e v e r t e b r a l a r t e r y ( V A ) u s i n g a n 81 m K r c o n t i n u o u s i n f u s i o n t e c h n i q u e 13,14 a n d h a v e s t u d i e d the a u t o r e g u l a t i o n a n d CO2 r e s p o n s e s o f t h e vessels in these r e g i o n s .
Clinical Materials and Methods Patients included are nine children and seven adults with Moyamoya disease. Five of the children were female and four were male, and ages ranged from 6 to 14 years. Except for one case in which onset was intraventricular haemorrhage, all had experienced transient ischaemic attacks. Among the adult patients, there were four females and three males, and ages ranged from 28 to 48 years. Onset in the adult cases was intraventricular haemorrhage in three cases, transient ischaemic attacks in three cases, and one asymptomatic case. In all cases, neurological symptoms were absent or mild at the time of CBF measurement. Cerebral blood flow was measured at two locations in each case, one in the region of perfusion of the ICA and one in the region of perfusion of the VA. Measurements were made after at least two months from onset and recordings from the ICA region were made at an interval of 1-2 weeks before or after those from the VA. The procedure was as follows: A catheter was led from the femoral artery and selectively placed in the ICA and VA. Following angiography, CBF measurements were made in the awake state. The blood flow measurements were made using the 81mKr continuous measurements technique TM14 81mKr extracted by passage of 5% glucose in Rb-Kr generator (Nihon Mediphysics), was continuously infused and radio activity was recorded at 10 sec intervals over the skull and cervical region using a gamma camera (Toshiba GCA 301) placed in prallel with the sagittal plane. Data analysis was done using a Toshiba GMS-80 A Data Processor. After the CBF was measured during rest, the vascular response was tested. Blood pressure was raised, then lowered, followed by
108
A. Ogawa etal.: Cerebral Blood Flow in Moyamoya Disease
C O 2 inhalation and hyperventilation. Hypertension was induced by venous drip of Angiotensin II for five minutes, causing an increase in blood pressure of 30-40 mmHg. Hypotension was induced by a venous drip of Trimethaphan, resulting in a decrease of 15~0 mmHg for about six minutes. Hypercapnea was produced by inhalation of 5% CO2 gas for four minutes. Hyperventilation was induced by instructing the patient to breath deeply for four minutes. During this entire period, blood pressure and blood gases were continuously monitored. In the analysis of the vascular response, study was made of the region of interest in the frontal lobe for the anterior circulation and in the occipital lobe and cerebellar hemisphere for the posterior circulation.In the autoregulation study, an autoregulation index (A % CBF/A BP) was calculated as the changes in blood flow during loading as compared to those during rest, while eliminating the effects of blood pressure changes. Similarly, in the study of the CO2 response, a CO2 response index ( • % CBF/& PaCO2) was calculated as the changes in blood flow, while eliminating the effects of PaCO2 change. For the evaluation of the results, those measurements in which sufficient changes in the blood pressure of PaCO2 were not obtained were excluded from the analysis.
A%CB%BP
Frontal lobe ~_ Occipital lobe Cerebellum
0
i ii
9
o
9
o
n=4 n--=-7 n=7
n=4 n=5 n=5
Child group
Adult group
Fig. 2. Autoregulation in response to hypotension
Results
l. Autoregulation in Response to Hypertension (Fig. 1) The autoregulation index scores in the frontal lobe, occipital lobe and cerebellum of the juvenile cases were 0.6 4- 0.59, 0.16 4- 0.27 and 0.26 4- 0.38, respectively. Although autoregulation was fairly well maintained in the cerebellum and occipital lobe, which are perfused by the VA, mild deficits of autoregulation were apparent in the frontal lobe, which is perfused by the ICA. In the adult cases, the autoregulation index scores were 0.74- 1.3, 0.094- 0.23 and 0.09 4- 0.23 in, respectively, the frontal lobe, occipital lobe and cerebellum. Similar to the juvenile cases, autoregulation was generally preserved in the cerebellum and occipital lobe,
Frontal lobe
A%CBF/~PaCO, Occipital lobe Cerebellum
6]
~
4-
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ol
20
0
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col m
-2-
n=4
n=5
n=5
Child group
Adult group
Frontal lobe Occipital lobe Cerebellum
1
"
--2"
n=7 n=7
Child group
perfused by the VA, but mild deficits were apparent in regions perfused by the ICA.
2. Autoregulation in Response to Hypotension (Fig. 2)
i
--1"
n=7
n=4
Fig. 3, CO2 response to hypocapnea by CO2 inhalation
A%CB~'~B p
i
n=5 n=4
n=6
n=7 n=7
Adult group
Fig. 1. Autoregulation in response to hypertension
The autoregulation index scores among the juvenile cases were - 0.8 + 0.73, - 0.76 4- 0.77 and - 0.87 4- l. 17 in the frontal lobe, occipital lobe and cerebellum, respectively. Autoregulation was disrupted at all of these sites. In the adult cases, the autoregulation index scores of the frontal lobe, occipital lobe and cerebellum were, respectively, - 0.08 + 1.68, - 0.32 4- 0.72, - 0.22 4- 0.35. Unlike the autoregulation in response to hypotension
A. Ogawa etal.: Cerebral Blood Flow in Moyamoya Disease
~%CBF/ /APaCO~ o
8-
Frontal
lobe
6-
Occipital lobe
4-
Cerebellum
20
-2. --
i
and cerebellum, perfused by the VA, was relatively favourable. Among the adult cases, these scores were - 1.22 4- 2.82, - 3.26 4- 0.7 and - 3.11 4- 1.03 for the frontal lobe, occipital lobe, and cerebellum, respectively. Three of the seven patients showed deficits in the frontal lobe, two of which were paradoxical responses. Normal responses were recorded from the occipital lobe and cerebellum.
Discussion
4-
o -6 --
109
m
8-
-10 -12-
.-
n=5 n=3 n=3
n=7 n=7 n=7
Child group
Adult group
Fig. 4. CO2 response to hypocapnea by hypoventi|ation
in the juvenile cases, that in the adult cases was relatively preserved.
3. The C02 Response to Hypercapnea (Fig. 3) The CO2 response index scores of the fronatl lobe, occipital lobe and cerebellum among the juvenile cases were, respectively, 2.4 + 3.06, 3.14 + 4.34, 1.8 i 2.46. Individually, two of four patients showed disappearance of the CO2 response in the frontal lobe, two of five in the occipital lobe, and three of five in the cerebellum. Among the adults, the CO2 response index scores were 2.86+1.79. 2.684-0.39 and 3.234-0.98 for the frontal lobe, occipital lobe and cerebellum, respectively. Individually, only one patient showed deficits of the CO2 response in the frontal lobe, indicating a considerably better situation than that found among the juvenile cases.
4. The C02 Response to Hyperventilation (Fig. 4) Among the juvenile cases, the CO2 response index scores were -0.984-6.14, -6.034-6.33 and - 5.88 + 6.47, respectively, in the frontal lobe, occipital lobe, and cerebellum. Two of the five patients showed deficits in the frontal lobe, one of which showed a paradoxical response. The response in the occipital lobe
The first study on the cerebral haemodynamics of Moyamoya disease was that of Takahashi et aL 27. In 1967, in which a NzO technique was used to measure the blood flow of the entire brain in six patients. Since then, various techniques have been used, including Xearterial infusion 9'28, Xe-venous infusion ~2'15, Argoninhalation 6, and recently three-dimensional PET scan 4. Debate has continued whether or not a reduction in cerebral blood flow occurs Moyamoya patients, but recently some consensus has been reached that, in comparison with normal children, there is a reduction in cerebral blood flow in juvenile Moyamoya cases. However, there have been no previous reports of the vascular response in this disorder and many uncertainties remain with regard to the underlying pathophysiology. We have previously reported details concerning our technique for making continuous measurements of changes in regional cerebral blood flow 12'16. In the present study, we have clarified certain aspects of the vascular response found in Moyamoya disease using this method. This method anables one to monitor serial changes in cerbral blood flow. By applying loads during such monitoring, it is possible to measure the changes in blood flow caused by specific conditions. For this reason, this method is particulary suitable for making measurements of the vascular response. It was found that the autoregulation in induced hypertension was relatively well-maintained in our patients. The autoregutation in the region of perfusion of the VA was especially well maintained, whereas deficits in the region of the ICA were not infrequent. In contrast, deficits in the response to hypotension were more often found than that to hypertension in both the regions of perfusion of the ICA and that of the VA. Particularly notable was the difference between the adult and juvenile Moyamoya cases in the autoregulation response to hypertension-the juvenile cases showing much stronger deficits. Nevertheless, usage of
110
the same technique for measuring autoregulation in other diseases has produced Autoregulation Index values in excess of 4-2.0, indicating that the deficits of autoregulation in both adult and juvenile Moyamoya disease are relatively mild. With regard to the CO2 Response Index, others have previously reported that normal subjects show values in excess of 1.0 and ranging between 2 and 42, 19,21. In the present study, we have found that a normal CO2 response to hypercapnea was maintained among the adult cases in both the region of the ICA and that of the VA. Abnormalities were found, however, in more than half of the juvenile cases. In response to hyperventilation, all of the adult cases showed normal responses in the region of the VA, whereas cases of paradoxical responses were seen among both the adult and juvenile cases in the region of the ICA. Moreover, among the juvenile cases there were also cases in which strong responses were seen both in the region of the VA and that of the ICA. In summary, there were mild but clear deficits in the autoregulation in response to hypotension and CO2 response to hypercapnea which, during the regulation of cerebral dynamics, require dilatation of blood vessels. These findings indicate that the regulated vessels, which control to vascular response, are in a state in which they cannot be dilatated. In a comparison of the autoregulation found in the adult and juvenile cases, it was seen that, despite the fact that the angiographic stage of the Moyamoya disease was more advanced in the adult cases, the deficits in the vascular responsiveness of the juvenile cases were greater. This difference is thought to be due to an intrinsic difference in the nature of adult and juvenile Moyamoya disease. That is, unlike adult Moyamoya disease, the onset in children usually involves ischaemic symptoms3,10,11,18 and there is normally a progression ot the vascular occlusive lesion in follow-up angiograms23'24'26. Moreover, there are conspicuous differences in the clinical picture of adult and juvenile Moyamoya disease25, such as the notable decrease in cerebral blood flow among the juvenile cases 12. The progression in the vascular occlusive lesion and the marked reduction in blood flow in comparison with normals suggests that the brain of the child with Moyamoya disease is in a continually ischaemic state. This conclusion is thought to be supported by the fact that, although relatively mild, the deficits of vascular responsiveness in juvenile cases are more severe than those in adult cases. It was also found that the deficits of responsiveness
A. Ogawa etal.: Cerebral Blood Flow in Moyamoya Disease
were more severe in the region of perfusion of the ICA than that of the VA. It is of course well-known that Moyamoya disease is a progressive, occlusive disorder of the ICA and that, in cerebral angiograms, blood supply is achieved through non-physiological pathways, such as through the medullary artery via the basal Moyamoya vessels, through the ethmoidal Moyamoya vessels via the ophthalmic artery or through the Vault Moyamoya vessels via the external carotid artery7. It is therfore thought likely that stronger deficits will arise in the region perfused by the ICA than that perfused by the VA. EEG studies in cases of juvenile Moyamoya disease have demonstrated the so-called "re-build up" phenomenon following hyperventilation1. All of the juvenile cases of the present study also showed such rebuild up. EEG redordings were not in fact taken during the haemodynamic measurements, but a tendency was found for a marked reduction in blood flow, particularly in the region of the VA. Within 5-10 minutes of the completion of hyperventilation, however, full recovery of cerbraI haemodynamics was seen. Moreover, in light of the fact that there were several cases which showed an increase in blood flow during and immediately after the hyperventilation in the region of the ICA, it is evident that the re-build up seen after hyperventilation cannot be explained solely as a reduction in blood flow. In fact, it has been reported that there is a suppression of breathing following hyperventilation, during which a decrease in the arterial PaO2 is observed 17, and that, following hyperventilation in juvenile Moyamoya cases, there is a decrease in oxygen consumption4. In the light of the above findings, we conclude that the vascular responses in Moyamoya disease are notably different both in adult and juvenile cases, and in the region of perfusion of the ICA and that of the VA. A variety of surgical treatment for Moyamoya disease, such as superior cervical ganglionectomy2~ 22 and vascular reconstruction5'8, have been reported, but their proper evaluation requires detailed study of the vascular responses following treatment.
References
1. KodamaN, AokiY, HiragaH, WadaT, Suzuki J (1979) Electroencephalographic findingsin children with moyamoyadisease. Arch Neurol 36:16-19 2. Iliff LD, Zilkha E, Du BoulayGH, MarshallJ, Russel RWR, SymonL (1974) CerebrovascularCO2reactivityof the fast and slow clearingcompartments.Stroke 5:607-611
A. Ogawa et al.: Cerebral Blood Flow in Moyamoya Disease 3. Isono M, Yonemitsu T, Fujiwara S, Kodama N, Suzuki J (1981) Epidemiological study on moyamoya disease: From the experiences of 100 cases. In: Proceeding of the 10th Japanese conference on surgery of cerebral stroke. Neuron, Tokyo, pp 3-7 4. Kameyama M, Shirane R, Tsurumi Y, Fujiwara S, Takahashi A, Suzuki J, Ito M, Ido T (1986) Cerebral blood flow and metabolism in childhood Moyamoya disease. An investigation into "re-build-up" phenomenon on EEG by positron CT, Child's Nerv Syst 2:130-133 5. Karasawa J, Kikuchi H, Furuse S, Kawamura J, Sasaki T (1978) Treatment of moyamoya disease with S T A - MCA anastomosis. J Neurosurg 49:679-688 6. Karasawa J, Kikuchi H, Kuriyama Y, Sawa T, Kuro M, Kobayashi K, Koike T, Mitsugi T (1981) Cerebral hemodynamics in "Moyamoya" disease. II. Measurements of cerebral circulation and metabolism by use of the argon desaturation method in pre- and post- neurosurgical procedures. Nenrol Med Chir (Tokyo) 21:1161 1168 7. Kodama N, Fujiwara S, Horie Y, Kayama T, Suzuki J (1980) Transdurai anastromosis in moyamoya disease: vault moyamoya. Neurol Surg (Tokyo) 8:729-737 8. Matsushima Y, Fukai N, Tanaka K, Tsuruoka S, Aoyagi M, Ohno K (1981) A new surgical treatment of moyamoya disease in children. A preliminary report. Surg Neurol 15:313-320 9. Nishimoto A, Ueta K, Kuyama H, Takemoto M, Arimitsu T, Mizukawa N (1976) Cerebral hemodynamics in moyamoya disease. In: Reports by the research committee on spontaneous occlusion of the circle of Willis. Japanese Ministry of Health and Welfare, Tokyo, pp 76-82 10. Nishimoto A, Takeuchi S (1967) Cerebral basal rete mirabile. In: Kudo T (ed) A disease with abnormal intracranial vascular networks. Spontaneous occlusion of the circle of Willis. Igaku shoin, Tokyo, pp 56-59 [in Japanese] I1. Nishimoto A (1979) Moyamoya disease. Neurol Med Chir (Tokyo) 19:221-228 12. Ogawa A, Kogure T, Fujiwara S, Kodama N, Suzuki J, Sakurai Y, Wada N (1981) Regional cerebral blood flow on moyamoya disease: study with 133Xe intravenous injection method. In: Proceeding of the 10th Japanese conference on surgery of cerebral stroke. Neuron, Tokyo, pp 189-194 13. Ogawa A, Sakurai Y, Suzuki J (1981) Continuous measurement of regional cerebral blood flow using 81mkrypton ' A preliminary report. Jpn J Nucl Med 18:329 331 !4. Ogawa A, Sakurai Y, Suzuki J (1983) Continuous measurement of regional cerebral blood flow using krypton-81 m. Stroke 14: 623427
111 15. Ogawa A, Sakurai Y, Kayama T, Yoshimoto T (1989) Regional cerebral blood flow with age: changes in rCBF in chiIdhood. Neurol Res. 11:173-176 16. Ogawa A, Yoshimoto T Suzuki T, Sakurai J (1990) Cerebral blood flow in moyamoya disease. Part 1: Correlation with age and regional distribution, Acta Neurochir. (Wien) 105:30-34 17. Ohyama H, Niizuma H, Fujiwara H, Suzuki J (1985) EEG findings in moyamoya disease in children-Concerning with causal genesis of re-build up. Neurol Surg 13:727-733 18. Ozawa E, Taneda M, Kataoka K, Ozaki K, Kaneda H, Irino T (1981) Moyamoya disease admitted as stroke. 10th Japanese Conference on Surgery for Cerebral Stroke: 217-220 19. Reivich M (1964) Arterial PCOz and cerebral hemodynamics. Am J Physiol 206:25-35 20. Sato S, Suzuki J (1975) Anatomical mapping of the cerebral nerve vasorum in the human brain. J. Neurosurg 13:559-568 21. Seki H, Yoshimoto T, Ogawa A, Suzuki J (1984) The CO 2 response in focal cerebral ischemia- Sequential changes following recirculation. Stroke 15:699 704 22. Suzuki J, Takaku A, Kodama N, Sato S (1975) An attempt to treat cerebrovascular "Moyamoya" disease in children. Child's Brain 1:193-206 23. Suzuki J, Kowada M, Asahi M, Takaku A (1965) Diseases showing the "fibrille" like vessels at the base of brain. Frequently found in Japan. Brain Nerve (Tokyo) 17:767-776 24. Suzuki J, Takaku A, Asahi M (1966) The disease showing the abnormal vascular network at the base of brain, particularly found in Japan. II. A follow-up study. Brain Nerve (Tokyo) 18: 897-908 25. Suzuki J, Takaku A (1969)Cerebrovascular moyamoya disease. Disease showing abnormal net-like vessels in base of brain. Arch Neurol 20:288-299 26. Takahashi A, Fujiwara S, Suzuki J (1985) Cerebral angiography following hyperventilation on moyamoya disease - In reference to "re-build up" phenomenon on EEG. Neurol Surg 13:255-264 27. Takahashi S, Kutsuzawa T, Takahashi S (1967) Studies on cerebral hemodynamics. In: Kudo T (ed) A disease with abnormal intracranial vascular networks. Spontaneous occlusion of the circle of Willis. Igaku shoin, Tokyo, pp 35-37 28. Uemura K, Yamaguchi K, Kojima S, Sakurai Y, Ito Z, Kawakami H, Kutsuzawa T (1975) Regional cerebral blood flow on cerebrovascular "moyamoya" disease: Study by 133Xe clearance method and cerebral angiography. Brain Nerve (Tokyo) 27:385-393 Correspondence and Reprints: Akira Ogawa, M.D., Division of Neurosurgery, Institute of Brain Diseases, Tohoku University, School of Medicine, 1-1 Seiryomachi, Sendai 980, Japan.
