Neureradiology

Neuroradiology 16, 228-232 (1978)

© by Springer-Verlag 1978

S e q u e n t i a l C h a n g e s o f R e g i o n a l C e r e b r a l C i r c u l a t i o n in C e r e b r a l I n f a r c t i o n K. Uemura I , K. G o t o I , K. Ishii 1 , Z. Ito 2, R. Hen 2 , and H. Kawakami 3 Departments of RadiologyI , Neurosurgery 2, and Internal Medicine 3, 6-10 Senshu-Kubota-machi, Akita, Japan

Summary. Sequential changes of regional cerebral circu. lation and effects o f spontaneous recanalization o f oc. cluded artery on cerebral circulation were observed in 50 patients with cerebral infarction. 1) Luxury perfusion was predominantly recognized in the recanalized patients within 16 days after onset. 2) Impairment o f vasomotor responses was almost the same in the recanalized patients and the occluded patients. 3) CO~ response tended to recover about 3 - 4 weeks after onset, but disautoregulation to induced hypertension persisted up to 2 months after onset. Some clinical problems are discussed.

Understanding o f regional cerebral hemodynamics in patients with cerebral infarction is important for the pathophysiological analysis o f cerebral infarction. Though several reports on pathophysiology o f regional cerebral circulation in patients with the disease are already available [2, 8, 9], little is known about its sequential changes after onset and the effects o f spontaneous recanalization o f occluded arteries in cerebral circulation. This paper describes the sequential changes o f regional cerebral blood flow (rCBF) and vasomotor responses in patients with cerebral infarction, and also the effects of spontaneous recanalization o f occluded cerebral artery on regional cerebral circulation.

Method The regional cerebral blood flow was measured in an affected hemisphere using 133Xe intra-arterial injection [6] and our highresolution Digital Auto fluoroscope system (Baird Atomic) [4] or a half-inch 16-channel multidetector system (Meditronics) [7]. rCBF examination was carried out under local anesthesia and started at least 30 min after the carotid angiography to avoid the effects on cerebral circulation of injecting opaque media. First, rCBF and mean hemispheric CBF (mHCBF) at resting state were measured by the height-over-area method [3, 6], and next, CO2 reactivity was obtained by inhalation of 5-7% carbon dioxide

(average elevation of Paco2. was about +5 mmHg). Finally, vascular response to briefly increasing blood pressure (about +30 mmHg on average) by intravenous injection of angiotensin amide was observed. In the~,high-resolution:system, , ~ B F and vascular response were display by the functional images in which more rCBF and vascular responses were indicated by larger squares [81.

Clinical Material Fifty patients, aged 34 to 72 years, average 59 years, were studied from 1 day to 2 months after onset. In 15 of the 50 patients, repeated rCBF examinations were carried out, so 69 studies were available for the analysis. Angiographic studies, which were made 123 times on the patients, initially showed proximal occlusion of the middle cerebral artery in 47 eases (94%). The others were branch occlusion of the middle cerebral artery or occlusion of the anterior cerebral artery. Partial or complete recanalization of occluded artery was verified by follow-up angiography in 20 cases (40%). With the angiographie findings, the patients were divided into two groups; the first group of 30 patients was the occluded group, and the second group of 20 patients was the recanalized group. All patients had a more or less severe hemiparesis of sudden onset, except three patients who had only aphasia. In both groups, about half of the patients revealed various degrees of unconsciousness at the acute phase. Eight patients (40%) of the recanalized group and four patients (13%) of the occluded group showed almost satisfactory remission of the symptoms. Moderate remission was recognized in five patients (25%) of the recanalized group and 11 (37%) of the occluded group. All the other patients showed only a poor remission of the symptoms and 2 patients (10%) of the recanalized group died of hemorrhagic infarction.

Results 1. Cerebral Circulation of the Occluded Group Cerebral Blood Flow at Resting State. mHCBF and rCBF of the group, correlated to time after onset, are presented in Figure la. All the studies, which were performed 38 times in the patients, showed sub normal values of mHC BF. These were 2 1 - 3 5 ml/100 g/min, average 28 ml/100 g/ min. Significant recovery o f decreased mHCBF was not

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K. Uemura et al.: Regional Circulation in Cerebral Infarction

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recognized for 2 months after onset. As presented in Figure la, most patients of the group revealed regional ischemia that had developed in the middle cerebral arterial distribution. Regional hyperemia with focal vasoparalysis (luxury perfusion) [2] was found in only three cases (10%), adjacent to the ischemic loci, and it appeared within 12 days after onset.

Vasomotor Responses. Impaired flow response to hypercapnea was recognized in 15 of the 19 patients tested within the first 14 days. In some patients, disturbance of the CO2 response was found in the area being perfused by the internal carotid artery (global disturbance). At 3 to 4 weeks after onset, normal response to hypercapnea was noted in four of the seven patients. Thereafter, dis-

turbance of the CO: response was no longer observed (Fig. 3a). With these results, we concluded that disturbance of COz response might begin recovery at about 3 to 4 weeks after onset. Disturbance of vascular response to induced hypertension was recognized in 19 of 20 patients who were examined for this within 14 days after onset and was observed globally in five patients (Fig. 3a). Four weeks after onset, nine of thirteen patients revealed disautoregulation. Even in the four patients studied between 47 days and 2 months after onset, focal disautoregulation was recognized. One of them showed complete recovery of the CO z response (Fig. 3a). Disturbed vascular response to induced hypertension seemed to persist longer than disturbance of the COz response. Disautoregulation

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K. Uemura et al.: RegionalCirculation in Cerebral Infarction 21

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and disturbance of CO2 response appeared in the ischemic foci, but their distribution was frequently not identical. Paradoxical flow response [2] was observed in three patients of the group (10%). Two patients studied at 2 and 16 days after onset respectively showed significant decrease ofrCBF to hypertension. Another patient tested 11 days after onset revealed decreased rCBF to hypercapnea, and he also showed regional hyperemia (Fig. 3a).

2. Recanalized Group Thirty-one rCBF examinations were carried out on the 20 patients of the group after verification by follow-up angiography of partial or complete recanalization of the occluded artery.

Cerebral Blood Flow at Resting State. Figure lb shows the sequential changes of mHCBF and rCBF in the recanalized group, The most prominent difference in cerebral circulation between the recanalized group and occluded group was frequent appearance of regional hyperemia (luxury perfusion) in association with recanalization of occluded vessels (Figs. lb, 2). Regional hyperemia was observed temporarily in 14 of the 20 patients (70%) within 16 days after onset. Mean hemispheric CBF of the affected hemisphere tended to increase, attended by regional hyperemia, but in the patients examined 4 weeks after onset, mHCBF of both groups were quite similar (Fig. lb). Incidence of

detection of ischemic focus in the recanalized group was lower than in the occluded group. However, the site of luxury perfusion turned ischemic at about 4 to 5 weeks after onset.

Vasomotor Responses. Figure 3b shows the sequential changes of vasomotor responses. There seemed generally no significant difference in sequential changes of vasomotor responses between the recanalized group and the occluded group (Fig. 3a and b). It was noteworthy that in sPite of almost complete recovery of CO2 response, a very disturbed vascular response to induced hypertension was observed in three patients who were examined by follow-up rCBF study within 18 days to 5 weeks after onset (Fig. 2). In hyperemic foci, COz reactivity was always disturbed, but vascular response to induced hypertension sometimes looked normal (Fig. 2). However, this might be caused by absence of vascular response, as there had already been maximal vasodilatation at resting state by vasoparalysis. Paradoxical flow response was observed infrequently in the group (five patients, 25%). Those observed during 3 to 13 days after onset were accompanied by regional hyperemia (Fig. 3b). Clinical Significance of Luxury Perfusion. Clinical significance of luxury perfusion has not been clearly explained. To elucidate the problem, correlation of luxury perfusion and prognosis of the patients was observed in the fairly uniform group, i.e., 18 patients with spontaneous

K. Uemura et al. : RegionalCirculation in Cerebral Infarction

231

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recanalization of proximal occlusion of the middle cerebral artery. Almost satisfactory recovery of neurologic deficits was recognized in three o f the five patients (60%) who did not show luxury perfusion, but We found only three of the twelve patients (25%) with luxury perfusion. It seemed that prognoses for neurologic deficits were poorer in the patients with luxury perfusion than in those without it. One patient out of the two groups (without

and with luxury perfusion) died of massive hemorrhagic infarction, which was verified by autopsy. Discussion As was also reported by Paulson et al. [8, 9] the majority of occluded patients in the series showed focal ischemia. This was infrequently seen in the recanalized group in

232 the acute stage. A tendency toward recovery o f decreased CBF in the occluded patients o f the present series was not recognized during the first 2 months after onset. rCBF in ischemic focus of the occluded patients with severe neurologic deficits decreased to 1 5 - 2 4 ml/100 g/ min, average 19.5 ml/100 g/rain. These flow values were a little higher than the experimentally observed threshold blood flow of normal brain [11]. Real flow value in the ischemic area was thought to be much lower than blood flow value measured by the laaXe method, because measured flow is dominated by the region receiving the most isotope [8]. In the present series, regional hyperemia (luxury perfusion) was actually observed in the recanalized patients: According to our finding, luxury perfusion is considered to be related mostly to recanalization o f occluded artery, i.e., reperfusion into the territory of previously occluded artery,where vasoparalysis dtae to brain:,,tissue acidosis is obvious. Paulson et al. reported that luxury perfusion in the infarcted brain was observed only within 2 days after onset [9]. However, in the present series luxury perfusion was observed up to 16 days after onset. Such a finding coincides well with our observation in cerebral angiography [13]. Four to five weeks after onset, the site of luxury perfusion turned out to be an ischemic lesion. The change ofhyperemic focus with time was considered to be due to decreased cerebral metabolism and recovery of vascular tone [5]. Paulson et al. reported that in a patient withmiddle cerebral arterial occtusion,~ focal disautoregulation persisted 1 month after onset. However, it has not been clarified how long vasoparalysis lasts. In the present study, CO2 response might recover at about 3 to 4 weeks after onset, but disturbance of response to induced hypertension persisted still longer. In four patients, focal disautoregulation was detected even 2 months after onset. The pathomechanism which causes persistence o f disturbance in vascular response to raised blood pressure remains to be cleared. Brain tissue acidosis might not be related to such disturbance in the chronic stage, because this might not last a long time. Increased cerebrovascular resistance caused by vascular occlusion and destruction of the vascular bed with hypoxia might be a contributing factor in shifting the lower limit o f autoregulation, to higher blood pressure. Spontaneous recanalization o f occluded artery has been known to occur frequently in the acute phase o f cerebral embolism [ 12]. The effect o f this phenomenon on cerebral circulation has not been clearly described. According to our observations described above, the most marked differences o f cerebral circulation between occluded patients and recanalized patients was frequent appearance of luxury perfusion in the latter group. However, sequential changes of vasomotor responses after onset showed no remarkable differences between the two groups. Clinical significance of luxury perfusion in the patient s with cerebral infarction was unknown [ 1, 14]. With our clinical observations in the present series, the prognosis o f neurologic deficits seemed poorer in patients with

K. Uemura et al.: Regional Circulation in Cerebral Infarction luxury perfusion. Recently, some neurosurgeons have attempted bypass operations on occlusive cerebrovascular disease [10]. Spontaneous recanalization might be regarded as offering a model for such operations. As to sequential changes o f cerebral circulation after onset, the present study did not reveal any significant difference between the occluded patients and the recanalized patients, except for luxury perfusion. Meanwhile, two patients of the recanalized patients died of hemorrhagic infarction within 2 weeks after onset. According to the results of the present study, it might reasonably be said that if one intends to perform a bypass operation on a patient with brain ischemia, the operation should not be performed within several weeks after onset. References 1. Heiss, W., Hayakawa, T., Waltz, A. G.: Pattern of changes of blood flow and relationship to infarction in experimental cerebral ischemia. Stroke 7, 454-459 (1976) 2. H~edt-Rasmussen, K., Skinli6j, E., Paulson, O., Ewald, J., Bjerrum, J. K., Fahrenkrug, A., Lassen, N. A.: Regional cerebral blood flow in acute apoplexy, the luxury perfusion syndrome of brain tissue. Arch. Neurol. 17, 271-281 (1967) 3. Kanno, l., Uemura, K.: Some experimental errors in calculating regional cerebral blood flow from the intracarotid 133Xe clearance curve. Stroke 6, 370-375 (1975) 4. Kanno,I., Uemura, K., Miura, Y.: A system measuring regional cerebral blood flow with a Digital Autofluoroscope and a small computer. Jpn. J. Nucl. Med. 13,183-192 (1976) 5. Lassen, N. A.: Control of cerebral circulation in health and disease. Circ. Res. 34, 749-760 (1974) 6. Lassen, N. A., lngvar, D. H.: Radioisotopic assessment of regional cerebral blood flow. Prog. Nucl. Med. 1,376-409 (1972) 7. Miura, Y., Uemura, K., Kanno, I.: A system for measurement of regional cerebral blood flow with Cerebrograph Model 165 and a small digital computer. Radioisotopes 25, 454-460 (1976) 8. Paulson, O. B.: Regional cerebral blood flow in apoplexy due to occlusion of the middle cerebral artery. Neurology 20, 73-77 (1970) 9. Paulson, O. B., Lassen, N. A., and SkinhCj, E.: Regional cerebral blood flow in apoplexy without arterial occlusion. Neurology 20, 125-138 (1970) 10. Schmiedek, P. (ed.): Microsurgery for stroke. Berlin - Heidelberg - New York: Springer 1977 11. Trojaborg, W., Boysen, G.: Relationship between EEG, regional cerebral blood flow and internal carotid artery pressure during carotid endoarterectomy. Electroencephalogr. Clin. Neurophysiol, 34, 61-69 (1973) 12. Watarai, J., Uemura, K., Okudera, T., Yamaguclii, K.: Angiographic findings of cerebral infarction in acute state: Analysis of follow up case in occlusion of the middle cerebral artery. Brain Nerve 28, 769-777 (1976) 13. Yamaguchi, K., Uemura, K. : Angiographic diagnosis of cerebral infarction. Jpn. J. Clin. Radiol. 21,127-135 (1976) 14. Yamaguchi, T., Waltz, A. G., Okazaki, H.: Hyperemia and ischemia in experimental cerebral infarction: Correlation of histopathology and regional blood flow. Neurology 21,565 to 585 (1971) K. Uemura, MD Department of Radiology Research Institute of Brain and Blood Vessels 6-10 Senshu-Kubota-machi Akita City, Akita, Japan