It is well known that the autoregulation of cerebral blood flow (CBF) is impaired in cerebrovascular disease (CVD). In addition, it is recognized that the autonomic nervous system plays an important role in the regulatory mechanism of CBF autoregulation. We have already reported the fluctuations of the autonomic nervous function in CVD, especially in its acute stage. However, no systematic evaluations of the relations between the time course of CBF autoregulation and autonomic nervous function have been attempted yet.
The present study was designed to investigate the dynamic changes in the time course of CBF autoregulation with relation to the autonomic nervous function.
The subjects of the present study were forty-two patients with hemisheric CVD except for cases with severe loss of consciousness and sixty normal controls.
CBF was estimated by using the method of cerebral arterio-venous oxygen difference. Changes in cerebral perfusion pressure were induced by head-up tilt method.
CBF autoregulation was quantitatively analyzed by means of dysautoregulation index, in other words, the ratio of changes in CBF was divided by changes in cerebral perfusion pressure.
The autonomic nervous functions were examined by using hemodynamic functional tests with simultaneous recordings of blood pressure, pulse rate and respiration.
Time course of CBF autoregulation was calculated by using high degree regression analysis.
The dysautoregulation indices, which were high immediately after the onset, decreased towards normal from the first to the fourth day. They moved higher from the fifth to the twelfth day, and returned towards lower values after the thirteenth day.
The degree of reflex bradycardia in Aschner's test, which is a parameter of the parasympathetic function, moved towards normal immediately after the onset. But, it had a poor response from the fifth day to the twelfth day, then once more it slowly returned towards normal after the thirteenth day. On the other hand, the time course of reflex hypertension in the cold pressor test, which is a parameter of the sympathetic function, showed abnormally high values on sixth and twentieth day after the onset.
Secondly, the relation of CBF autoregulation to autonomic functions were investigated in the cases with acute CVD. Aschner's test showed a poor response in the cases where the dysautoregulation indices had abnormally high values. In contrast to this, Aschner's test had a good response in the cases where the dysautoregulation indices were normal. On the other hand, the time course of reflex hypertension in the cold pressor test did not show any close connection with CBF autoregulation in acute CVD.
The above data suggest that the parasympathetic nervous function has a strong correlation with CBF autorevulation.

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Since preventive therapies for cerebral ischemia hasn't fully been established, safe control of anticoagulant and antithrombotic treatments was investigated. In patients of cerebral ischemia, hyperactivity of blood coagulation or platelet aggregation is frequently encountered. If it can be suppressed or controled in normal level, second attack of cerebral infarction might be prevented. Anticoagulant therapy was performed to 40 cases of cerebral ischemia. For maintaining the value of thrombo-test in a range between 10 to 20%, the best administrative method of Warfarin without hazard is considered as follow : Day 1, 15 mg, Warfarin p.o.; Day 2, 12 mg; Day 3, no administration; From Day 4, 3 mg, daily as maintenance dose. Mean dosage of Warfarin was 4.7 mg/day. The thrombo-test should be carried out every day during the treatment for detecting hemorrhagic tendency. By this therapeutic procedure, second attack of cerebral infarction was completely prevented without hemorrhage.
In case of antithrombotic therapy without measurement of platelet aggregation activity, a case of subarachnoid, intracerebral hemorrhage and 4 gastric bleedings were encountered. Hemorrhage was, however, completely prevented in cases under control by platelet aggregation test.
For maintaining in suitable range of platelet aggregation activity of patients, Aspirin adminiation should be adjusted to obtain the activity in a range between a normal level (the second aggregation occurred by a final concentration of 3 μM ADP), and slightly suppressed level (5 μM ADP). In 68.6% of the cases, 200 mg/day of Ticlopidine hydrochloride was enough to obtain desirable clinical effect. 300 mg/day of the drug was rarely needed.
Under therapeutic procedure, second attack of cerebral infarction was completely prevented without hemorrhage. Anticoagulant and antithrombotic agents can be safely administered under careful measurement of both thrombo-test and platelet aggregation activity. Those therapeutic procedures are valuable and recommended for preventing second attack of cerebral ischemia.

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To elucidate the significance of cerebrospinal fluid pressure (CSF pressure) on the development of symptomatic normal pressure hydrocephalus after subarachnoid hemorrhage, continuous monitoring of lumbar CSF pressure was done via the thin polyethylene catheter in 28 cases of subarachnoid hemorrhage with or without symptomatic normal pressure hydrocephalus for 8 to 16 hours including night. The baseline pressure was defined as the mean pressure two hours after catheterization. There were three groups based on the symptomatology; asymptomatic group (A group, 7 cases), group of symptomatic normal pressure hydrocephalus (B group, 16 cases) and group of markedly impaired consciousness (C group, 5 cases).
The baseline pressure was 13.1 ± 5.1 mmHg in A group, 15.9 ± 7.6 mmHg in B group and 20.4 ± 13.7 mmHg in C group. It was higher in B and C groups, though statistical significance was not obtained. There was a general tendency that the pressure wave was more frequent in the higher baseline pressure. B wave was dominant comparing to A wave. In the A group, three of seven cases showed low baseline pressure with no or minimal pressure wave. However, there was two cases which had high baseline pressure of 20 mmHg and four cases of pressure wave; frequent B wave in three and sporadic A wave in one.
In the B group, the pressure wave was noted in all five cases of baseline pressure above 15 mmHg and in six of eleven cases of normal pressure. The higher the baseline pressure, the more the frequency of B wave. There was a tendency of periodic burst of B wave, which was more clearly seen in cases of relatively low baseline pressure. It was noted that there were three cases of low baseline pressure without pressure wave, although clinical symptoms and CT findings were consistent with typical normal pressure hydrocephalus. All of thirteen shunting operations were effective in this B group.
In the C group, the vaseline pressure was varied in each case, pressure wave was noted in cases of high pressure, although A wave noted in one case of low baseline pressure. Shunting operation was effective in three of five case in this C group.
Thus, there are some cases in which correlation of CSF pressure raising and development of symptomatic normal pressure hydrocephalus was not noted, although high baseline pressure and/or frequent B wave were the common finding in them. The importance of brain damage was discussed in conjunction with impaired CSF circulation and CSF pressure.

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Through the angiographical study of the progress in pediatric moyamoya disease, a typical clinical model of a chronic progressive ischemia in the young brain, we proposed a hypothesis that the brain is surrounded by several systems of collateral networks arranged in rather concentric fashion and that the anatomical characteristics of the head prevent the use of some of the systems as collaterals at early stage of cerebral ischemia. The anatomical characteristics include the presence of a watery layer of subarachnoid space between the cortical and dural vessels and a bony closed box intervening between the dural and scalp arterial networks. They isolate the brain from the abundand blood flow of the external carotid system as if they were the moat (subarachnoid fluid layer) and the walls (skull) of a castle.
Based upon these concepts, we have developed a surgical procedure, the encephalo-duro-arterio-synangiosis (abbreviated as EDAS) for the treatment of moyamoya disease in children. This operation surmounts the above mentioned two obstacles to the formation of the collaterals to the brain via the external carotid system, by perforating the castle walls and bridging the moat by wound granulation without injuring the already formed natural collarerals.
We performed this operation on 70 sides in 38 pediatric moyamoya patients and various degree of revascularisation of the brain was obtained in 100% of the cases with proportionate improvements of the symptoms.
According to the philosophy as stated above, EDAS should be available not only for the moyamoya disease but also for the chronic ischemia to the brain other than moyamoya disease. Accordingly, we prformed this operation to a patient who presented with acute infantile hemiplegia and revealed to have a complete obstruction of the left carotid artery at C1 portion. This patient showed marked revascularisation of the left hemisphere by the implanted left STA 10 months after the operation. This is one of the clinical evidences that spontaneous EC/IC anastomoses can be formed in other ischemic condition than moyamoya disease just by surmounting the above mentioned two obstacles by surgical procedure.
We conclude that an indirect EC/IC anastomotic procedure like EDAS can be applicable to other cerebrovascular ischemic conditions than moyamoya disease.

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Regional cerebral blood flow (rCBF) was measured by ¹³³Xe inhalation technique during acute (Day 1-Day 14), subacute (Day 15-Day 28), and chronic (Day 29-) stage in 68 cases with embolic and 63 cases with thrombotic cerebral artery occlusion. All cases had unilateral supratentorial ischemic events. Diagnostic criteria of embolic and thrombotic cerebral artery occlusion have been reported elsewhere (Jpn Circ J 48 : 50, 1984).
In thrombotic group, mean rCBF of the affected hemisphere was significantly lower than that of the unaffected side, and was fairly constant in all stages (p<0.001). In contrast, mean rCBF of the affected side of embolic cases was significantly lower than that of the unaffected side only in subacute and chronic stages (p<0.02, p<0.001, respectively). Furthermore, mean rCBF of the affected hemisphere in acute stage was significantly higher than that in chronic stage (p<0.02).
When mean rCBF of each case in acute stage was plotted against that in chronic stage, a significant positive correlation was obtained in either hemispheres in both groups. Regression lines of thrombotic cases were approximately equal to the line of Y=X, while mean rCBF of embolic cases in acute stage was higher than that in chronic stage, making regression lines Y=0.47X + 23.1 in the affected hemisphere, and Y=0.74X + 11.0 in the unaffected hemisphere.
Regional CBF of the ischemic hemisphere was expressed as %CBF of corresponding channel in the contralateral hemisphere (relative rCBF). More than 40% of total number of channels showed relative rCBF higher than 100%, and only 21% showed decreased relative rCBF less than 90% in acute stage of embolic group. In chronic stage, these percentage changed to 23% and 50%, respectively. In thrombotic group, 58% of total channels showed the relative rCBF lower than 90% even in acute stage, and regional patterns of CBF showed no significant difference during the course.
High rCBF in acute stage of embolic group was thought to be the reflection of an increase of blood flow after reopening of the previously occluded artery that is frequently observed in embolic cerebral artery occlusion.
From the results of the present study, it is concluded that sequential changes of regional blood flow in cases with embolic cerebral artery occlusion are quite different from those with thrombotic cerebral artery occlusion; i.e., increased rCBF of the affected hemisphere in acute stage of cerebral embolism, and more constant and pronounced decrease of CBF in all stages of cerebral thrombosis.

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In the management of subarachnoid hemorrhage in acute stage, neurological grading was the standpoint of discussion so far. However, the location and volume of hematoma are better revealed by CT scan. The prognosis varies between intracerebral hematoma and cisternal hematoma even in cases of the same neurological grading, due to vasospasm. Therefore, the management is better discussed under CT grading. 254 cases had been operated by the same neurosurgeon from September 1976 to August 1982. 61 cases were treated conservatively because of severe grade, vasospasm, rebleeding while waiting for operation etc. Therefore 315 cases make the subject of this study. Preoperative neurological grading, CT findings, operative timing, occurence of symptomatic vasospasm and outcome were evaluated. (1) Operative mortality was 2% in delayed operation (more than 2 weeks). (2) Symptomatic vasospasm occured in 40% of cases operated between 24 hours and 2 week and in 8-12% of cases of very early operation (within 24 hours) and in cases of delayed operation. (3) Incidence of symptomatic vasospasm was closely related to the volume of hematoma in the basal cistern. But symptomatic vasospasm seldom occured when operated within 24 hours, even though there was much hematoma in the basal cistern. (4) All cases of grade V died when they were treated conservatively. (5) Comparing very early operated cases with other cases, very early operation cases showed statistically significant survival rate in grade IV, lesser incidence of vasospasm in grade III and better outcome in cases worse than grade III. Therefore, the golden hour in treatment of SAH is within 24 hours. Earlier operation is indicated even in worse cases for better outcome.

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Rats with experimental cerebral ischemia were prepared by clipping bilateral carotid arteries for 30 minutes after bilateral vertebral arteries of Wistar rats had been electrocauterized. The activity of 5'-nucleotidase was measured quantitatively in brain homogenate and also demonstrated histochemically. The activity of 5'-nucleotidase was detected mainly in the pia mater and slightly in the white matter, but not in the arterial wall of Wistar rats which received a sham operation. The enzyme activity was demonstrated also in the surrounding part of cerebral arteries in rats which showed a complete paralysis brought about by the occulusion of four vessels.
The activity of 5'-nucleotidase in brain homogenate was significantly higher in rats with a complete paralysis (29.8 ± 5.2 nmoles/mg protein/min) than either in rats without paralysis (23.3 ± 3.8 nmoles/mg protein/min) or in rats with a sham operation (22.0± 4.1 nmoles/mg protein/min) (p<0.05).
These results suggest that adenosine is produced by the increased activity of 5'-nucleotidase in the periarterial region of rats with cerebral ischemia and adenosine would cause a dilatation of arteries as a compensatory mechanism for cerebral ischemia.

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In 27 cases with primary pontine hemorrhage over a period from October 1979 to April 1983, we studied the correlations between clinical signs, computed tomographic findings and prognosis. The cases were consisted of 23 males and 4 females between 31 to 65 years with average age 50.0. They could be classified into four groups according to the clinical courses. 1) group of good recovery : ADL I, II (9 cases), 2) group of severe disability : ADL III, IV (3 cases), 3) group of death with complications (3 cases), 4) group of early death (12 cases). On admission, comatous state, ocular fixation, absence of light reaction and tetraplegia or decrebrate posture were the signs of bad prognosis. Respiratory disturbance was not always the sign of early death. In fact, three patients with abnormal respiration were in group of good recovery. On the CT, the horizontal extension of the hematoma was demonstrated by the diameter of the hematoma on the transverese section through the pons, and vertical extension was indicated by the number of slices (10 mm in width). The hematomas of the group of good recovery were less than 25 mm in diameter, and they were seen on less than 3 slices. The hematomas lager than this size were seen exclusively among the groups of death and severe disability. Furthermore, the rupture of hematoma into the IVth ventricle was the sign of bad prognosis. All cases were treated conservatively. We emphasize the importance of prevention of complications and respiratory care in the management of the pontine hemorrhage.

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Doppler ultrasonic imaging (DUI) and oculoplethysmography (OPG) were applied to evaluate the usefulness for detecting the extracranial carotid occlusive disease in 163 arteries of 96 patients.
When the results of each noninvasive technique were compared independently with the findings of conventional carotid angiography, overall diagnostic accuracy of DUI was 82.2% and that of OPG 81.6%. False positive and false negative rates were 11.3% and 33.3% in the former, and 10.4% and 37.5% in the latter, respectively. Thus, there was no difference in diagnostic accuracies between two techniques.
If the positive findings of at least one of either methods were taken into account, false negtive rates decreased by approximately 20% (from 33.3% and 37.5% to 14.6%), although overall diagnostic accuracies remained unchanged (81.6%).
Among 23 carotid arteries with stenosis more than 50%, which were thought to be hemodynamically significant, 20 arteries were diagnosed by DUI, and 22 arteries by OPG. All 23 arteries were diagnosed as having significant stenosis by combination of both techniques.
No complication was observed in patients who underwent both DUI and OPG.
DUI and OPG are easy to perform, have extreamely low risk of complication, and have high diagnostic sensitivity, especially for hemodynamically significant stenosis. The present results indicate that the combination of these two techniques are more useful for screening of patients with possible carotid occlusive disease.

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The present study was designed to investigate the cerebral blood flow (CBF) autoregulation and its relation to hypertrophy of arterial wall during development of hypertension in young spontaneously hypertensive rats. Unilateral superior cervical ganglionectomy was performed to examine the effects of sympathetic nerves on CBF regulation. Hydrogen clearance method was used to measure CBF and wall/lumen ratio was estimated with freeze-substitution technique.
Basal blood pressure were 88 mmHg at 4 weeks of age, 105 at 6 weeks and 127 at 9 weeks, and CBF were 51, 51 and 48 ml/100 g/min, respectively. The upper limits of CBF autoregulation were 109 mmHg, 126 and 168 in these rats, being correlated well with increase in basal blood pressure. In acutely denervated hemisphere, the upper limits were significantly lowered from 109 to 100 mmHg at 4 weeks and from 168 to 151 mmHg at 9 weeks. Chronic denervation (2 to 5 weeks after ganglionectomy) did not affect the autoregulatory range. The wall/lumen ratios of cerebral arteries were 0.133 at 4 weeks and 0.130 at 9 weeks, of which difference being not significant. Sympathetic denervation did not alter the ratio.
These results indicate that 1) upward shift of the CBF autoregulation with age is closely related to rise in basal blood pressure without evidence of increase in vascular hypertrophy, and 2) acute interruption of sympathetic nerves impairs the autoregulatory capacity during acute elevation of systemic blood pressure.

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To elucidate when blood vessel with spasm becomes functionally irreversible in terms of physiological function of vasoconstriction-vasodilation is believed to be an important guideline of selecting an adequate therapeutic method for cerebral vasospasm.
We studied the relation of behavior of electrical discharge of vascular smooth muscle with isometric vascular contraction and histological change of vascular wall in order to know the functional reversibility of blood vessel with spasm by using cerebrovascular specimens of 27 human autopsy cases that had died of SAH or other diseases. Grouping discharge and sporadic discharge were detected in 7 and 4 cases of non-SAH group (13 cases) respectively, indicating good vascoconstriction. No evidence of muscle necrosis were disclosed histologically. Contrarily, grouping discharge was not detected in SAH group (14 cases), excepting that sporadic discharge was detected in 5 cases with local narrowing of the blood vessel. Muscle discharge and vascoconstriction were rarely seen in the cases with prolonged cerebral vasospasm while extensive muscle necrosis was observed. Muscle discharge was detected in those who died within a week after the onset of cerebral vasospasm or those with local narrowing of the blood vessel. It seemed likely that the functional reversibility of blood vessel with spasm is lost at about one week after the onset of cerebral vasospasm.
The efficacy of a calcium antagonist, diltiazem, on cerebral vasospasm was evaluated in 26 cases with intracranial aneurysm. In general, following an intravenous one shot of 20 mg of diltiazem, 60 mg per day was infused continuously by intravenous drip for 7 successive days. In therapeutic group, improvement of clinical symptoms including disturbance of consciousness, hemiplegia and aphasia and relief of cerebral vasospasm were obtained in 4 of the 8 cases with cerebal vasospasm resulting from SAH and 7 of the 9 cases with postoperative cerebral vasospasm. The clinical symptoms began to improve at 24-72 hours after starting the medication and the improvement preceded complete relief of cerebral vasospasm. The effectively treated cases were limited to those who were started on diltiazem therapy within 5 or 6 days after the onset of cerebral vasospasm. Those who received the drug more than 6 days after the onset of the symptom failed to respond to the drug. this result is in good agreement with the result of a fundamental study which demonstrated that the functional reversibility of blood vessel with spasm is lost at about one week after the onset of cerebral vasospasm.
Mild cerebral vasospasm occurred in 2 cases of preventive group (9 cases), but the symptom progressed in very slight or asymptomatic state.
It is concluded that calcium antagonist therapy should be initiated in the early stage of cerebral vasopasm or the drug should be administered to prevent the onset of cerebral vasospasm.

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We reported a case of paramedian thalamic and midbrain infarcts. A 46-year-old man was admitted to our hospital because of disturbance of consciousness with urinary incontinence. He had aortic regurgitation and hypertension in his past histories. His family history was normal.
Physical examination on admission showed blood pressure 200/100 mmHg, pulse rate 22/minute, regular, diastolic murmur on the 4th left sternal border.
Neurological examination revealed as follows. His consciousness was somnolent. He could state his name, years and day by our asking. But the other words were too unclear to understand. He always closed his eyes. Downwards gaze was impossible. There was no nystagmus but doll's eye phenomenon could be elicited. Snout and jaw reflexes were exaggerated. There was hemiparesis bilaterally, which was prominent at left extremities. Muscle tone was more decreased at left extremities. Pathological reflexes were elicited bilaterally. There was hemisensory disturbance at left extremities. He showed urinary incontinence.
Laboratory data were normal. Lumber cerebrospinal fluid was normal. ECG showed no arrhythmia. Echocar-diogram showed aortic valve dilation but there was no echogenicity of thrombi. EEG showed diffuse slow alpha activities, alpha blocking and slightly mixed theta waves. Brain CT scan revealed butterfly-like low density areas in both thalami and well-defined low density area in the right mesencephalon. Vertebral artery angiogram showed the occlusion of the right basilar communicating artery.
We though this case a brainstem infarction and treated conservatively. He was improved gradually, however, showed fluctuation. Hypersomnia and abnormal behavior became disappeared. He could gait without help, get his speech back. But his intelligence remained to be decreased. Vertical gaze paralysis was remained. Involuntary movement appeared on the right hand lately.
We thought that this case was a paramedian thalamic and midbrain infarcts (Castaigne). Reffering some cases which similar clinical signs, we thought that the paramedian thalamic and midbrain infarcts were different from akinetic mutism and were special syndrome caused by the selective occlusion of the basilar communicating artery which has many variabilities of its perforating arteries.

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Primary pontine hemorrhage caused by vascular malformation is considerably rare in adults, especially above 50 years old. Case report. A 57 years old man admitted to the hospital because of sudden onset of vertigo, vomiting, headache and weakness of the left extremities on Feburuary 7, 1984. Blood pressure was 136/70 mmHg on add-mission. Neurological examination revealed consciousness disturbance (lethargy), neck stiffness, mild left sided hemiparesis, right sided ataxia, conjugate deviation of the eyes to the left and right sided Homer's syndrome. CT scan revealed small localized hematoma in the right upper pontine tegmentum associated with massive ventricular hemmorrhage (Fig. 1). Two days after the admission, his consciousness level was declined. CT scan revealed marked obstructive hydrocephalus (Fig. 2). Conservative anti-brain edema therapy was effective and he became alert following two weeks. Cerebral angiography revealed small arteriovenous malformation which was feeded from right superior cerebellar artery (Fig. 3). Enhanced CT scan examined 3 months after the onset showed a small enhanced spot in low density area in the right lateral tegmentum of the upper pons (Fig. 4). These findings indicated that the cause of pontine hemorrhage in this case was rupture of the arteriovenous malformation.

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