In 8 patients with brainstem vascular accidents who were admitted within 48 hours after the onset, the activity of dopamine-β-hydroxylase (DBH) in peripheral venous plasma was analyzed applying the method described by Nagatsu and Udenfriend. The plasma sample were serially collected every a few days for a month after the onset.
Plasma DBH activity was 27.5 ± 12.0 and 16.5 ± 8.0 (mean ± S.D.) units/litter of plasma, on the admission and the 28th day after the onset, respectively. The activity within 48 hours after the onset showed the highest value throughout the observation period of a month and tended to decline time-dependently for a month. The patterns of time course of plasma DBH activity after the onset revealed no relationships with the severity of the disease and activities of daily living which was evaluated a month after the onset.
These results suggest that, in brainstem vascular accident, the noradrenergic nervous function was stimulated in acute stage of the disease and gradually suppressed for a month without regard to its size and location in contrast with cerebral hemispheric vascular accident.

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Protective effects of barbiturates against ischemic brain damage have been widely accepted in animal experiments. However, there is no controlled study on this treatment in human cerebral infarction.
In the present study, high dose barbiturate therapy was carried out in patients with acute cerebral infarction. To evaluate clinical effects of the treatment, CT findings and outcome of the patients in the treated group were compared with those of the control group. In addition, size of infarction and degree of mass effect were related to the time of onset of the treatment.
Nine patients with embolic occlusion of the major cerebral vessel were treated with barbiturate as soon as possible after the insult. Sites of occlusion in these patients were as followings; the internal carotid artery (ICA) in 4, the middle cerebral artery stem (MCA stem) in 2 and multiple major cerebral vessels (multiple) in 3. Diagnosis of cerebral embolism was made if there was an abrupt onset, and if an embolic source and/or evidence of systemic embolization were present. The control group consisted of 57 patients with embolic cerebral artery occulsion treated conventionally without barbiturate; ICA in 25, MCA stem in 17 and multiple in 15. The ratio of the largest hypodense area to the largest hemispheric area on CT (expressed in %) was used to indicate the size of the infarction (Infarct Index). The ratio of degree of the midline shift to the hemispheric width in CT (expressed in %) was also used to indicate the degree of mass effect (Midline-shift Index).
In the treated group, 500-1, 000 mg of sodium thiopental were injected intravenously, then tracheal intubation was performed. Depth of anesthesia was maintained at the level of suppression and burst pattern on EEG, with continuous intravenous infusion of thiopental under controlled respiration and careful circulatory monitoring for 24-48 hours.
Mean Infarct Index was smaller in the treated group than in the control group (22.2% and 41.9%, respectively), but the difference was not statistically significant (0.05<p<0.1). The difference of the Midline-shift Index between the treated and the control group (5.8% and 12.1%, respectively) also did not reach the statistically significant level. The former was smaller than the latter. Number of death within 2 weeks after the insult was only one in the treated group, and 17 out of 57 cases in the control group. Ultimate survival rate during the observed periods was 89% in the treated group and 56% in the control group. Difference of a functional outcome of survived patients between two groups was difficult to evaluate because of small number of cases in the treated group. Significant positive correlations were observed between the onset of barbiturate therapy and the Infarct Index (r=0.677, n=9, p<0.05), and the Midline-shift Index (r=0.698, n=9, p<0.05).
In this preliminary human study, possibilities of protective effects against ischemic brain damage and of an amelioration of survival rate in patients with severe cerebral embolism were suggested, if barbiturate therapy was started very early after the insult.

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Hyperventilation is a well known method of reducing the raised ICP and has been used widely in clinical practice. The mechanism of reducing ICP is believed due to the cerebrovascular contraction resulting in the decrease of cerebral blood volume.
Little has been known about the dynamics of rCBF of the white matter during hyperventilation under the presence of mass lesion. The purpose of this study is to clarify the relationship between rCBF of the white matter with mass lesion and the various levels of PaCO₂ produced by hyperventilation in dogs.
Epidural balloon compression of the brain was employed as simulating the model of intracranial mass lesion, which was placed in the right frontal area. Platinum electrode for hydrogen clearance determination of rCBF was stereotaxically inserted into the white matter of the left frontal lobe. ICP was monitored by subdural balloon technique, which was placed in the left occipital area. After the measurement of control value of rCBF, the epidural balloon was inflated and CIP was maintained at 40 mmHg for 77 minutes. Then, rCBF was measured in three different levels of PaCO₂, normocapnia (40 mmHg), mild hypocapnia (30 mmHg) and severe hypocapnia (20 mmHg) produced by mild and extreme hyperventilation. rCBF measurements without compression were also performed for control group, under the same PaCO₂ levels as in the epidural compression group.
Significant reduction of rCBF of the white matter (17.2 ± 3.2 to 12.6 ± 3.7ml/100 g/min) was recorded after the epidural balloon inflation. In the epidural compression group, rCBF of the white matter was decreased to 64% of control value at mild and 53% at extreme hyperventilation. rCBF in control group was decreased to 78% at mild and 69% at extreme hyperventilation. The raised ICP (40 mmHg) was reduced to 30.7 mmHg by mild and 28.6 mmHg by extreme hyperventilation.
It can be concluded that hyperventilation in a case with intracranial mass lesion may be a method of choice to reduce raised ICP, but rCBF of the white matter may easily decrease below the critical level. Extreme hyperventilation should be avoided, since the further reduction of ICP can not be expected and there is a danger to induce the ischemic insult of the white matter.

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Since the discovery of opiate receptors in the central nervous system, there have been a few reports which indicated an important role of endogeneous opiate substances in cerebrovascular diseases. The purpose of the present study is to investigate the effects of pure opiate antagonist, naloxone, on experimental ischemia in gerbils.
Under light anesthesia with sodium pentobarbital, the right common carotid artery was ligated and the all animals were decapitated two hours after the ligation. One hundred and eighty nine animals were used in the present study.
Unilateral common carotid artery ligation produced neurologic deficits, i.e. hemiparesis, abnormal circling behavious, in about one third of the animals.
After the intraperitoneal injection of naloxone (1 mg/kg), transient reversal of ischemic neurologic deficits, which started within three to five minutes and lasted about fifteen minutes, were observed.
Regional cerebral blood flow measured by hydrogen clearance method decreased with naloxone administration in the sham operated animals. By contrast, cerebral blood flow significantly increased after the naloxone injection in the carotid ligated animals with neurologic deficits, in which cerebral blood flow was already diminished before the administration of the agent.
The animals with neurologic deficits showed a marked increase of both water content and Na/K ratio in the ischemic hemisphere, but these abnormal findings were improved by the administration of naloxone. In the contralateral hemisphere of the same animals, a significant but less remarkable increase of water content and Na/K ratio was also observed. The administration of naloxone resulted in a significant decrease of NaiK ratio but no change in water content of the contralateral hemisphere. Injection of naloxone made no significant changes in arterial blood pressure, Pao₂, Paco₂ and pH.
These findings suggest that naloxone improves both cerebral metabolism and brain edema in the acute stage of cerebral ischemia with the antagonistic effect on the opiate substances which are known to increase in the ischemic brain. Furthermore, these data may indicate a possible role of the opiate system in the reduction of cerebral metabolism observed in the contralateral hemisphere.

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The neuropathological findings of acute severe cerebral infarction was analyzed in comparing with four autopsied cases and our experimental cerebral infarction in dogs. Four autopsied comm with acute severe cerebral infarction were 1 male and 3 females ranging in age from 57 to 68 years. All patients gave the history of hypertension and cardiac disease. Of all death, 3 of the 4 patients died within 7 days after clinical evidence of infarction. In 3 patients, angiography showed an occlusion of internal carotid or middle cerebral artery and a recanalization. A CT-scan was performed in 3 patients.
Experimental cerebral infarction was induced in 165 dogs by injecting one or two silicon rubber cylinder through the cervical internal carotid artery. The embolus was found to have obstructed the main trunk of the middle cerebral artery in 102 dogs. Horizontal sections of each brain were shown by carbon perfusion 24 hours after embolization. Large sized infarction of the cerebral hemisphere showing a large carbon perfusion defect in the cerebral cortex, the cortical and deep white matter, and in the basal ganglia were represented in 47 dogs.
The results obtained were as follows :
1. Pathologic changes of the autopsied and experimental case were resembled closely, and the gross specimens and histologic sections were reviewed that the massive hemorrhagic area was localized in the basal ganglia region and the petechial hemorrhagic area in the corticomedullary junction region of the infarct afecting the hemisphere in the middle cerebral artery distribution. It is suggested that the massive hemorrhagic infarction may be caused by the disruption of the arteriole in the perforating arterial terminal zone, and the petechial hemorrhagic infarction by the disruption of the venule in the cortical arterial terminal zone.
2. The CT of the patient with fatal cerebral infarction showed only large low-density area with a negative contrast enhancement which occupied the affected hemisphere almost entirely and which also showed large mass effects. Acute severe cerebral infarcts appear as low density area, with lower attenuation values due to the presence of large amounts of fluid, therefore the addition of blood in hemorrhagic infarcts of the basal ganglia and the corticomedullary junction may be negative on CT scan. Acute severe cerebral infarction appear in the CT image as low density areas due to marked edema, hewever, a histological correlation is not concomitant.

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Effects of nifedipine, the most potent Ca-antagonist used for management of hypertensive emergencies, on cerebral hemodynamics in CVDs were investigated by the Ar inhalation method. A single oral dose of 10 mg of nifedipine reduced mean arterial blood pressure (MAP) from 130 ± 20 mmHg to 119 ± 22 mmHg (p<0.05) in 8 cases of acute cerebral hemorrhage and from 108 ± 32 mmHg to 90 + 20 mmHg (p<0.05) in 5 cases of chronic ischemic cerebrovascular diseases, respectively. However, no significant changes of CBF and CMRO₂ were observed in both groups. The changes of CBF had no relationship with dysautoregulation of cerebral circulation confirmed by lowering cerebral perfudion pressure by head tilting. Nifedipine also reduced peripheral vascular resistance measured in 5 cases, while cerebral resistance remained unchanged in these patients before and after administration of the drug. In a single case of thalamic hemorrhage, intraventricular pressure (IPV) was monitored, and a gradual increase of IVP from 9 mmHg to 19 mmHg was observed 45 minutes after administration of the drug. In 2 cases, therefore, effects of nifedipine on cerebral circulation with and without a simultaneous intravenous administration of glycerol (10%, 200 ml) were compared, and marked increases of CBF were observed by combined administrations of nifedipine and glycerol.
These findings suggest that nifedipine has a direct dilatatory effect on cerebral vessels, but that CBF remained unchanged possibly due to elevation of intracranial pressure caused by cerebral vasodilation or the differences of vascular susceptibilities to Ca-antagonists.

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Noradrenergic innervation of the cerebral arteries has been histochemically and electronmicroscopically established. However, the direct evaluation of its function has never been attempted yet.
Recently we succeeded in demonstrating the action potentials directly from the cerebral arterial walls of the cat. Discharges of the action potentials increased during induced hypotension and decreased during induced hypertension. These responses of the action potentials were affected by the intravenous administration of various agents such as a ganglion blocking agent (hexamethonium bromide), a dopamine-β-hydroxylase inhibitor (fusaric acid), a false neurotransmitter (5-hydroxydopamine) and an axonal conduction inhibitor (tetrodotoxine).
The purpose of the present study was to investigate the effects of cervical sympathectomy on the action potentials and their responses to changes in blood pressure.
Twenty adult cats were anesthetized with 1.0% a-chloralose and 10% urethane followed by artificial respiration. Superior cervical ganglionectomy and preganglionectomy were performed in 7 and 13 cats, respectively.
Action potentials from the pial arterial walls were recorded by means of fine bipolar platinum electrodes, high sensitive. preamplifiers, band-pass filters and a data analyzing computer. Mass discharges of the action potentials were analyzed using a program of pulse density variation.
Preganglionectomy did not abolish the normal responses of the action potentials to changes in blood pressure ( : an increase of the discharges during induced hypotension and a decrease during induced hypertension) in 6 out of 7 cats for acute experiments. The normal response was maintained even three weeks after the operation in 5 out of 6 cats for chronic experiments.
Immediately after the superior cervical ganglionectomy the normal response of action potentials to changes in blood pressure was maintained in all cats except one. On the other hand, three weeks after the operation the response was completely abolished on the side of the operation in all 4 cats, although the response on contralateral side was remained intact.
In conclusion, the response of the discharges directly recorded from the pial arterial walls was abolished in the chronic cats with superior cervical ganglionectomy, which suggests that the superior cervical ganglion plays some role on the action potentials from the pial arterial walls.

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The infuence of social activity on regional cerebral blood flow (rCBF) and mental function was studied by Xe 133 inhalation method in normal aged volunteers.
Subjects : The first group consisted of 33 aged volunteers living in nursing home and exposed to little social stimuli. There were 15 males (mean age of 77 years) and 18 females (77 years). The second group consisted of 49 aged community volunteers who were confirmed socially active. There were 25 males (76 years) and 24 females (72 years). All subjects were healthy persons without a past hitory of cerebral diseases and lung diseases. There were no difference in blood pressure and hematocrit between the two groups.
Method : The rCBF was measured by 16-ch-Novo-cerebrograph. Verbal intelligence was evaluated by the Hasegawa Simple Intelligence Scale for Aged. Performance intelligence was evaluated with the Kohs' Block Design Test.
Results : 1) The mean rCBF in group I showed significantly lower value than that of group II, especially in the frontotemporal region. The performance intelligence was decreased in group I. However, there were no significant difference in the verbal intelligence between the two groups. 2) The aging effect on rCBF and intelligences was more prominent in group I than in group II. 3) In males, hemispheric rCBF of group I decreased bilaterally associated with the decrease of both intelligences. While the left hemispheric rCBF in females was relatively preserved as well as the preservation of verbal intelligence.
These results indicate that the social environmental factors may have significant influence to aging of the brain especially in the males.

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One rare case in which thrombus in an unruptured intracranial aneurysm was suggested to have caused cerebral embolisms is described.
The patient is a 38-year-old house wife who has neither complications of hypertention, heart diseases, angitis or diabetes nor risk factors such cigarette smoking, oral contraceptives or abnormal coagulation activity. Following a stroke, left homonymous quadrantanopsia and left thalamic syndrome were observed. CT-scan revealed small low density area in the right thalamus and in the right occipital lobe. Cerebral angiogram by Seldinger's method showed a fusiform aneurysm (7 mm x 15 mm) in the left vertebral artery and an aplasia in the right vertebral artery.
In this case it should be said that the cerebral infarctions in thalamus and occipital lobe were caused as a result of an embolism originating from a thrombus in a non-ruptured aneurysm of the vertebral artery. The genesis of the fusiform aneurysm in this case seemed to be influenced by the aplasia of the right vertebral artery caused by an unusual blood flow in the basilar artery. A review of the literature has been done in regard to the relation between ischemic cerebrovascular diseases and an unruptured aneurysm.

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Two cases of thalamic hemorrhage with monochoreo-athetosis were reported.
The first case was 74-year-old woman who addmitted by choreoathtosis of right leg. She had experienced transient right hemiparesis and loss of consciousness one month before addmission. One week before addmission, monochoreo-athetosis appeared suddenly. On addmission, neurological examination revealed only mild increase of muscle tonus and choreo-athetosis in right leg. CT showed small low density area in left thalamus (Fig. 1). This choreo-athosis was disapeared one month after the addmission.
The second case was 77-year-old man who addmitted by monochoreoathetosis of left leg. Neuological examinations at admission revealed otherwise normal. CT showed small high density area in right thalamus (Fig. 2AB). Choreo-athetosis was dissappeared one month after the addmission. By the mapping on the atlas of Schaltenbrand-Bailey, the lesion of the first case was supposed to be located in ventro-lateral thalamic nucleus and that of the second case could be located in ventral intermediate thalamic nucleus (Fig. 3AB). Cases of pure antero-lateral thalamic syndrome with monochoreo-athetosis like our cases are considerably rare.

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Cerbral venous angioma is said to be one of the most common anomalies of intracranial blood vessels found at autopsy. However, reports of cases with symptoms and clinical verification of angioma are rather scanty.
The present paper contained two cases of cerebral venous angioma diagnosed on the basis of characteristic findings of their cerebral angiograms.
Case 1 : A 45 year-old female was admitted because of gait-and left upper limb ataxia. In 1955, she was excised a subcutaneous angioma like tumor on the left side of the forehead. On August 22, 1982, she noticed unsteady gait and clumsiness of the upper limb on volitional movements. During preceding three weeks, she had three episodes of dull headache with slight fever, both of which had subcided within a day. Neurological examinations on admission revealed no abnormalities except for cerebellar signs.
Computerized tomograms of the brain (CTs) showed a low density area (LDA) in the cerebellar vermis, in which a curvi-linear high density area (HDA) was visualized by contrast enhancement. The left vertebral angiograms were normal in the arterial and capillary phases, but in the venous phase, they showed numerous fine medullary veins which flew into an enlarged draining vein; possibly left hemispheric or inferior vermian vein.
Her symptoms rapidly disappeared after parenteral administration of mannitol. The LDA gradually diminished, but there were no changes in the contrast enhanced HDA.
Case 2 : A 39 year-old male visited our hospital on November 4, 1981, because of headache which suddenly appeared two days before. Neurological examinations revealed no abnormalities.
Brain CTs showed a small round HDA in the right frontal subcortical region. After the contrast enhancement, a linear HDA was demonstrated in the same region. Right carotid angiograms demonstrated no abnormalities in the arterial and capillary phases. The venous phase showed many medullary veins in the right frontal lobe. They were drained into an enlarged frontal ascending vein.
His headache subcided soon after the conservative therapy. The HDA in plain CTs disappeared after about 10 months, while the use of contrast media still visualized the linear HDA.
Based on these two patients and 46 cases in the literature, clinical manifestations in cerebral venous angioma and its angiographic characteristics were discussed.

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Thalamic hemorrhage of the dominant hemisphere has been known to lead to abnormalities of language. However, the role of thalamus in language function and the pathophysiology of language disorders following a damage of the thalamus in the dominant hemisphere remain controversial. Recently, main clinical pictures of language disturbances following left thalamic hemorrhage has been recognized to be similar to the “transcortical” aphasia.
In this report, two patients with left thalamic hemorrhage who showed clinical pictures of the transcortical sensory aphasia were presented. A 62-year-old and a 66-year-old male were admitted to the National Cardiovascular Center with complaints of slightly disturbed consciousness, motor weakness of right extremities and no verbal output. Computed tomographic examinations revealed left thalamic hemorrhage with rupture into the ventricles in both patients. Language disturbances in the acute stage were characterized by paucity of spontaneous speech with diminished voice volume, marked disturbances of verbal comprehension and intact repetition with echolalia.
The Standard Language Tests for Aphasia (SLTA) that were performed two months after the insults revealed pronounced disturbances of verbal comprehension with paraphasia and perseveration. Agraphia and acalculia were apparent. Although almost all modalities of language function were impaired, ability of repetition was characteristically preserved. They were able to repeat a sentence with several words completely and fluently. Results of the SLTA suggested that language disturbances in these two patients were consistent with those of the transcortical sensory aphasia.
Measurements of regional cerebral blood flow by 133Xe inhalation technique revealed pronounced ischemia in the left parieto-temporo-occipital region in the first case and diffuse ischenia in the left cerebral hemisphere in the second. Topographical mapping of the electroencephalography showed depletion of alpha and beta components and predominance of diffuse theta and delta components especially in the left cerebral hemisphere.
The pathophysiologic mechanisms of the transcortical aphasia following the left thalamic lesion were discussed.

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