Of 260 patients with ruptured intracranial aneurysm, symptomatic vasospasm occurred in twenty-eight patients.
The existence of a high density area spanning the bilateral cisterns on CT is significant as an index of vasospasm and of prognosis.
To prevent the occurrence of vasospasm, we used ventriculo-cisternal drainage (VCD) in patients with ruptured intracranial aneurysm in the acute stage.
This VCD method made it possible to decrease the incidence of vasospasm, especially in the cases operated within 48 hours after SAH.
The frequency of the shunt operation for NPH was indifferent with VCD or without VCD.

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To treat ruptured aneurysm in acute phase, spinal drainage was performed in all patients except for a few who already showed signs of tentorial herniation. Spinal drainage was placed on the day of admission and flow rate was strictly controled 5ml-10ml/hr, which means about 200ml CSF was removed per 24 hours. Surgical treatment was done usually on the second day. Spinal drainage was removed at about 7 days after operation. The result was quite satisfactory. Although temporary or mild vasospasm was encountered, no severe vasospasm causing permanent morbidity was experienced. Morbidity was attributed to temporary blood flow shut down over 15 minutes or low blood pressure under 60 mmHg in systolic pressure during surgery. Over 80 percent of patients were discharged without any neurological deficit.

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Treatment of subarachnoid hemorrhage in the acute stage is still controversial. Nicardipine, one of Ca⁺⁺ antagonist, is considered to have vasodilating effect on cerebral arteries. Some favorable experimental results of effectiveness of nicardipine on cerebral vasospasm has been reported.
Authors evaluated the effect of cisternal irrigation with nicardipine-Ringer solution (0.01mg/ml) to prevent human cerebral vasospasm.
In 16 cases with 3 or 4 CT group operated upon within 48 hours after subarachnoid hemorrhage due to cerebral aneurysm, irrigation was carried out for 14 days on an average after aneurysmal clipping. As nicardipine is concentration dependent agent, it is necessary to keep effective concentration of nicardipine during irrigation. Cisterno-cisternal irrigation was performed from sylvian cistern and/or interhemispheric cistern to prepontine cistern, instead of ventriculo-cisternal irrigation, with which nicardipine is diluted by cerebro-spinal fluid.
Symptomatic vasospasm was found in 50% of 16 cases. In 62% of cases vasospasm was observed in at least one of three main branches; i. e., anterior cerebral artery (Al), middle cerebral artery (Ml) and internal carotid artery (Cl). Half of cases were excellent or good results and no fatal case due to vasospasm was found. These results were compared favorably with our 185 reported cases without nicardipine irrigation.
Cisternal irrigation with nicardipine may prevent vasospasm and improve the prognosis of severe subarachnoid hemorrhage due to ruptured aneurysm.

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In six subarachnoid hemorrhage cases due to ruptured anerysm, effects of cisternal administration of Nicardipine hydrochloride (nicardipine) on vasospasm were studied. Nicardipine was one of Ca antagonists. All aneurysms were clipped within 48 hours after the onset of subarachnoid hemorrhage with ventricular and cisternal drainages. Subarachnoid clot was removed as much as possible.
Nicardipine or mixture of nicardipine and urokinase was administered through cisternal drainage every day for 10 days postoperatively. The dose of nicardipine was 2 mg or 4 mg, and that of urokinase was 6,000 units or 24,000 units. In two cases cisternal drainages were slipped out naturally on 9th and 6th day postoperatively, so further administration of nicardipine was not possible.
On the 7th day after the onset of subarachnoid hemorrhage, angiography was performed two times before and 30 minutes after cisternal administration of nicardipine. Then the diameters of vessels were compared each other in order to estimate the vasodilative effect of nicardipine.
In almost all cases vasodilative effect of nicardipine could not be observed whether vasospasm occurred or not. But this did not always point out this drug to be ineffective. In this study nicardipine was considered to have some prophylactic effects to vasospasm because vasospasm was not observed either angiographically or clinically in 2 of 3 severe subarachnoid hemorrhage cases on CT, the outcomes of those cases were estimated as good recovery.

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Calcium antagonists acting directly on the vascular smooth muscle have recently been reported to be effective for prevention and treatment of cerebral vasospasm. These agents, however, generally induce reduction of systemic blood pressure when administered intravenously, and this hypotensive action of calicium blockers, even that of diltiazem, cannot be ignored especially in the presence of intensive hypertension.
We attempted to combine topical high-concentration administration of a vasodilator with cisternal drainage by attaching a polymer of diltiazem and silicone to the tip of the drainage tube. Results of in vitro and animal experiments were reported previously. In this report, results of clinical trials are presented. Subjects consisted of 14 patients with ruptured cerebral aneurysm aged 35-67 years who underwent surgery 0-4 days after the rupture. The patients were classified according the scale of Hunt and Hess as Grade I (5 patients), II (3), III (4), or IV (2), and SAH scale of Fisher as Grade I (1 patient), II (3), III (8), or IV (2).
In general, the concentration of diltiazem in the cerebrospinal fluid (CSF) reaches a peak (5ng/ml/mg), 15 minutes after a bolus intravenous injection, and that during continuous intravenous infusion of 2-3μg/min/kg of body weight is 150-200 ng/ml in serum and 10-20ng/ml in CSF. The concentration in the cisternal drainage fluid attained by our method 1, 5, and 10 days after the surgery was 2-10, 0.4-6, and 0.25-1.2ng/ml/mg, respectively. The concentration tended to be high in patients with lesions of higher grades or showing CT images of massive subarachnoid hemorrhage, but was unaffected by the daily amount of the drained fluid.
One grade III patient died, but the remaining 13 patients all showed favorable outcome. Prognosis appeared to be unrelated to the grading or the amount of hemorrhage, but the number of cases was too small for valid statistical analysis.
The present method is considered to be of additional value for examining serial changes in the condition of the CSF or direct monitoring the intracranial pressure.

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This study reports the effect of intracisternal administration of papaverine in 15 patients with vasospasm due to rupture of aneurysm. All patients had undergone clipping of aneurysm and had neurological deterioration and had decreasing level of consciousness. Bolus injection of 40mg of 1% papaverine hydrochloride was started on day 6.3±1.7 and continued for 4.4±1.6 days.
In seven cases serial angiogram after initial dose revealed dilatation of IC and/or anterior, middle cerebral arteries at 30 min and further dilatation up to 85% increase in diameter at 60 min, which continued at least 90 min. Arteries with marked vasospasm responded more to papaverine than those with less vasospasm.
In all but two cases vasodilatation tended to become prominent by report doses, twice a day, for two to seven days. Vasodilatation was observed only in IC and proximal trunks of ACA and MCA where papaverine could make direct contact, but not in the distal branches beyond A3 or M3. Neurological examination showed improvement of paresis or level of consciousness in 7 cases but no effect in 6 cases. Intracerebral hematoma occurred in two cases during the treatment.
Therefore intracisternal papaverine is the treatment of choice in cases with symptomatic vasospasm with some cautions on concentration to be administered.

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Computer tomographic analysis was done in 120 patients who were hospitalized in Hunt & Kosnik's grade I-III within 24 hours of SAH and, without undergoing operation within 15 days of SAH, presented uncomplicated natural course of vasospasm.
The analysis demonstrated that patients with severe (attenuation number 70 or more) high density in the basal cistern almost always developed severe vasospasm. Their outcomes are: fair 27%, poor 13%, dead 60% in patients with local severe high density, and poor 17%, dead 83% in patients with diffuse severe high density.
These patients, coupled with these data, served as controls in assessing the effect of systemic heparin which was administered in other 5 patients with severe cisternal high density. In the latter 5 patients, aneurysm surgery combined with irrigation drainage of blood contaminated CSF was performed within 24 hours of SAH and, after 24 hours of operation, systemic heparin was started at loading doses of 5,000 units followed by maintenance doses of 15,000-20,000 units/24 hours. Supplementary treatment was 2,000-3,000ml mild hypervolemic infusion with 600-1,000m/glyceol. Coagulation studies including PT, APTT, Fibrinogen, thrombo test, FDP, and antiprothrombin III were done up to 15 days of heparin treatment.
Outcomes of the patients treated with heparin are: good 1, fair-poor 1 in patients with diffuse severe high density, and good 1, fair 1, dead 1 in patients with local severe high density. Neither hemorrhagic complications nor abnormalities in coagulation studies were encountered in the treatment with heparin. These results appeared to support recent experimental works suggesting that heparin not only has an anticoagulant property, but has a property of reducing proliferative angiopathy in vasospasm.
The authors are under further investigation of this anti-proliferative action of heparin, using arterial smooth muscle cells in culture.

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Cerebral vasospasm would be one of the most hazardous problems in acute surgery of ruptured aneurysms at present. If only the ultra-early stage operation could completely remove the subarachnoid clots, which are considered to be the main cause of vasospasm, there would be no possibility of vasospasm. Total removal of the clots, however, is technically impossible so far. We attempted not only to dissolve and eliminate the blood clot but also to change the spasmogenic substance into something that has no harm.
We have already reported our experimental studies on vasospasm at the Conference of Surgical Treatment of Stroke in 1985. Its summary was as follows: 1) 120 IU/ml urokinase (UK) was most effective in dissolving clots. 2) Oxyhemoglobin (oxyHb), recognized as one of the spasmogenic substances derived from blood, was changed to the unknown resolved products by ascorbic acid (AsA) in vitro. This change was clarified on absorption curve. 3) These products from oxyHb did not induce vasospasm in acute phase experiment of cats. According to these experimental studies, we have clinically performed the cisternal irrigation therapy with UK and AsA following ultra-early surgery for ruptured aneurysms.
Thirteen cases were chosen among the patients of ruptured aneurysms who have come to our clinic since May 1984. These patients were all in Group III according to Fisher's classification in CT scan and their CT number was over 60, which suggested great possibility of vasospasm. The ages ranged from 36 to 74. According to Hunt & Kosnik, 7 were in Grade II, 5 in Grade III, and 1 in Grade IV. Acom anerysms were 5, MC AN 4, IC AN 3 and AC AN 1. Two or three tubes were inserted to both or either Sylvian fissure and chiasmal cistern depending on the site of subarachnoid clots, and the irrigation with lactated Ringer's solusion was performed at the speed of 20-40 ml/hr. The duration of this irrigation therapy was between 6 to 12 days (mean 8.8 days). UK was administrated 12 hours after the operation and its concentration was 120 IU/ml. AsA(2-4mg/ml) was added from 4 days after onset in 8 cases. CT scan was repeated during irrigation to observe the changes of subarachnoid clots. The outflow of drainage was taken every day and measured in RBC, Hb, FDP and absorption curve.
In 12 cases out of 13, no symptomatic vasospasm was found. One patient developed a slight hemiparesis immediately after stopping the irrigation, but was discharged with no deficit and returned to the normal life. During irrigation, cell proliferation in cerebro-spinal fluid was found in some cases, but did not lead to infection nor any severe complication. The number of the cases is not still enough to prove the effect of our therapy. Cisternal irrigation therapy with UK and AsA, however, might be considered one of the effective methods to prevent vasospasm following ultra-early surgery for the ruptured aneurysms.

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The effect of removal of subarachnoid blood clots on the prevention of delayed ischemic deficit was evaluated in 242 patients with ruptured supratentorial aneurysms, which were clipped within 48 hours after subarachnoid hemorrhage (SAH) via a pterional approach. They were all classified preoperatively in Grade 1 to 4 according to the system of Hunt and Hess. Severe delayed ischemia which caused permanent disability or death occurred in 32 (30.8%) of 104 Group A patients in whom blood clots only adjacent to the aneurysms were removed. It occurred in 17 (12.3%) of the other 138 Group B patients in whom subarachnoid clots were more radically removed along the arteries around which the arachnoid membrane could be opened as extensively as possible at least by way of a unilateral pterional approach. In Group B, the clots around the middle cerebral artery (MCA) ipsilateral to approach were most extensively removed up to the distal portion beyond the trifurcation. The incidence of delayed ischemia in the area of the MCA ipsilateral to approach was 22.1% in Group A and 5.8% in Group B. Its incidence in the area of the other arteries than the MCA ipsilateral to approach was 8.7% in Group A and 6.5% in Group B. The results in this study indicate that extensive removal of subarachnoid clots decreases occurrence of delayed ischemia due to vasospasm.

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The efficacy of the operation for the ruptured cerebral aneurysm within 6 hours after subarachnoid hemorrhage is compared with the operation performed between 6 and 24 hours after subarachnoid hemorrhage in terms of the surgical outcome, the normalization of cerebrospinal fluid (CSF) myelin basic protein(MBP), the degree of the removal of the subarachnoid blood clots (SABC) in cisterns, and the incidence of the intraoperative rupture of the aneurysm.
CSF was taken from the ventricle at the operation and from the ventricular drainage 14 days after operation. And the assay of the CSF MBP was done according to Cohen et al. MBP under 4 ng/ml is reported as negative.
30 patients (27-74 years, mean 52 years) were operated on within 6 hours after subarachnoid hemorrhage (ultra early operation group), and 18 patients (26-72 years, mean 51 years) were operated between 6 and 24 hours after subarachnoid hemorrhage (early operation group). The former included 2 patients in Grade I, 6 in Grade II, 12 in Grade III, and 10 in Grade IV. The latter included 2, 3, 7, and 6 patients respectively. CSF MBP was measured in 3 patients in Grade I, 3 in Grade II, 15 in Grade III, and 14 in Grade IV. MBP was negative in the patients in Grade I or Grade II except for one with 5ng/ml. In Grade III, however, MBP ranged from 8 to 120 ng/ml, and in Grade IV it ranged from 28 to 650ng/ml. The incidence of MBP over 100 ng/ml was 20% and 79% respectively (P<0.01), by X² corrected for small number, which showed a fairly good correlation of the elevation of MBP with the severity of subarachnoid hemorrhage. Normalization of MBP on the 14th day after subarachnoid hemorrhage was found in 15 of 18 patients (83%) in Grade III or IV in the ultra early operation group, and 4 of 11 patients (36%) in Grade III or IV in the early operation group (P<0.05), which means early normalization could be brought about by theultra early operation. 28 of 30 patients by the ultra early operation had no neurological deficit or need no help in a daily life, and 15 of 18 patients did the same by the early operation. All of three dead cases exceeded 70 years of age.
Subarachnoid blood clots (SABC) were classified on CT according to Fisher et al. Removal of SABC was evaluated as effective when ++ became + or -, or + became-. SABC was removed in almost all sylvian cisterns on the operation side and prepontine cisterns in the both group. The incidence of the removal of SABC in the interhemispheric fissure was 17 of 22(77%) by the ultra early operation and 5 of 15 (33%) by the early operation (P<0.02). As for the sylvian cistern contralateral to the operation side, the incidence was 11 of 16 and 5 of 11 respectively with no statistical significance. The incidence of the intraoperative rupture of the cerebral aneurysm was 4 of 12 middle cerebral artery aneurysm and 3 of 8 anterior communicating artery aneurysm in the ultra early operation group, and in the early operation group the incidence was 3 of 7 and 2 of 5 respectively. Intra operative rupture of the internal carotid artery aneurysm was not encountered in the both group.

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The effects of subarachnoid clot evacuation for the prevention of vasospasm (Vs) in the acute stage were reported previously at the 11th Conference of Surgical Treatment of Stroke in 1982, and complications due to excessive brain compression were pointed out when extensive clot evacuation was applied to the angry, swollen brain. In this paper, incidence of Vs demonstrated by angiography, neurological signs (NS) due to symptomatic Vs and low density area (LD) on CT scan which indicated ischemic infarction due to Vs was studied and compared with that of the previous report which dealed with 121 cases from 1976 to 1981.
Materials were 71 cases of ruptured aneurysm who were admitted within 3 days after the onset of subarachnoid hemorrhage (SAH) from 1982 to 1984. CT scan and angiography were followed for evaluating Vs and LD. Cases of intracerebral hematoma, troubled operation, moribund appearance and more than 70-year-old were excluded. In 12 cases out of 24 who revealed NS, neurological deficits disappeared at the time of leaving hospital. One case died of brain swelling with herniation due to Vs. The incidence of Vs, NS and LD were 85%, 34%, and 17%, respectively in this study. Vs and NS did not reveal definite changes, but LD revealed definite decrease, compared with the previous results of 80%, 39%, and 26%, respectively. The severer the degree of SAH, the higher the incidence of Vs, NS, and LD. On the other hand, the more marked SAH, the more decrease NS and LD. These results would indicate that the present policy for the treatments of SAH has been reasonable.
In the acute stage of SAH, sedation after neurological short evaluation and control of blood pressure should be performed preoperatively for the prevention of rebleeding attacks. Aneurysmal operations should be carried out as soon as possible if better prognosis was expected, especially in severer cases. Minimal brain retraction and sharp dissection could be the most important principle in the operations, and subarachnoid clots could be evacuated under minimal brain compression not to worsen brain conditions. Therapy with hypertension, hypervolemia and administration of dehydrates, Ca⁺⁺ antagonist etc is performed in the early postoperative stage, and will have an effect on symptomatic Vs.
The incidence of brain infarction following Vs decreased as a result of (1) advancement in the operative procedures with the most important principle of minimal brain retraction and sharpdissection, and (2) treatment or prevention of symptomatic Vs in the early postoperative stage.

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The hemorheological changes following SAH were observed to resolve the cause of disturbance of microcirculation induced by vasospasm. Among the factors influencing upon the blood viscosity, (1) aggregation of red blood cell, (2) erythrocyte deformability, (3) platelet adhesiveness, and (4) blood coagulability were studied. All the factors observed showed a tendency to accelerate the blood viscosity following vasospasm in SAH. The use of several drugs showed the useful result to reduce this hyperviscosity condition. The therapeutical trial from the aspect of hemorheology might be one of the most important approach to improve the deteriorated cerebral microcirculation following vasospasm.

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The clinical effects of diltiazem on cerebral vasospasm were evaluated in 38 patients with ruptured intracranial aneurysm. The drug was administered for therapeutic purpose of cerebral vasospasm to 21 cases (Group 1: 10 with associated cerebral vasospasm due to subarachnoid hemorrhage (SAH) and 11 with vasospasm after radical operation). The drug was also given for preventive purpose of postoperative development of vasospasm to 17 cases without arterial spasm in preoperative angiogram (Group 2). In general, 20 mg of diltiazem was initially administered by intravenous bolus injection, followed by continuous drip infusion of 60 mg per day for 7 days. Relief of vasospasm was evaluated by angiogram taken at suitable intervals under observation of clinical symptoms.
The following results were obtained.
1) Following administration of diltiazem, clinical symptoms such as disturbance of consciousness, hemiplegia, and aphasia were improved in 12 (57.1%) of the 21 cases of group 1.
2) Improvement of clinical symptoms appeared between 24 and 72 hours after administration of diltiazem, which preceded complete relief of cerebral vasospasm.
3) Diltiazem was more effective on postoperative vasospasm than on vasospasm occurring after SAH in group 1. The drug was ineffective in most of the patients with such SAH acute complication as primary brain damage, brain swelling or acute hydrocephalus, and in whom intracranial pressure was severely elevated. A trend was seen for diltiazem to be less effective in patients over 65 years of age than younger patients.
4) Many cases responded to diltiazem satisfactorily when the medication was initiated within 5 or 6 days after the onset of vasospasm, while the drug was practically ineffective when it was started a week or more after the onset of vasospasm.
5) The efficacy of diltiazem was correlated closely with timing of medication rather than with severity of cerebral vasospasm; the correlation was detected in cases with more than 40 ng/ml of the blood drug level.
6) Cerebral vasospasm manifested in 4 of the 17 cases of preventive group (group 2). Of these 4 cases, 1 suffered from transient hemiparesis while 3 progressed asymtomatically.
7) Protective effect of diltiazem on the formation of ischemic lesion was evaluated in 103 control cases without diltiazem administration and 21 cases that received diltiazem treatment. There was no great difference in the incidence of infarction between the control and therapeutic group. As for extent of infarction, the lesion in the therapeutic group tended to be small in comparison with the control group.
From this study, we can suggest that administration of diltiazem for the treatment of vasospasm should be instituted in the early stage after the onset of vasospasm or the drug should be prescribed for prevention of the onset of vasospasm.

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Our previous report demonstrated that platelet cyclooxygenase activity and serum dopamine-β-hydroxylase activity in patients with subarachnoid hemorrhage (SAH) due to ruptured aneurysms gradually increased, reaching a maximum value on Day 7 following the onset, coincided with the occurrence of vasospasm.
This study of human platelet cyclooxygenase, using an assay system measuring the thiobarbituric acid reaction, shows that dopamine-β-hydroxylase can trigger a rapid acceleration of cyclooxygenase activity to produce thromboxane A₂ (TXA₂).
These results suggest that an adrenergic mechanism plays an important role in the microcirculatory damage induced by lipid peroxidation during the occurrence of vasospasm following aneurysmal SAH.
The present study was further designed to find successful treatment for delayed spasm. Our previous study demonstrated that isosorbide dinitrate (1, 4: 3, 6-dianhydro-D-glucitol dinitrate, ISDN) was not only an inhibitor to both cyclooxygenase and dopamine-g-hydroxylase, but also a radical scavenger.
In our present study, topical application of ISDN (50 ng/ml) caused relief of experimental vasospasm in the cat basilar artery induced by 5 min topical application of incubated blood which obtained as a micture of an equivalent volume of blood and CSF incubated at 37°C for 3 days.
Topical application of ISDN (50 ng/ml) also caused relief of human constricted pial arteries on Day 3 following aneurysmal SAH. From the present study, ISDN is considered to relieve the microcirculatory damage due to vasospasm following aneurysmal SAH.
Our method of ISDN administration is to attach an ISDN adhesive tape preparation (40mg) on the chest, which is changed every 12 hours. The period of administration shall continue until the 14th day after occurrence of the intracranial aneurysm rupture.
In case of early operative intervention, 50ng/m/ ISDN 10 l is administered topically during the operation after clipping. If appearance or aggravation of ischemic symptoms is foreseen due to vasospasm, in spite of ISDN application, 50 ng/ml ISDN 10 ml is additionally administered into the cavity of the cerebrospinal fluid.

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Nowadays, cerebral ischemia due to angiospasm was treated with several drugs. However, we were not able to find most available treatment, yet.
We used Fluosol DA-20 and dopamine for treatment of ischemic symptoms perhaps due to angiospasm and got following data from neurological examination and rCBF studies, repeated CT scans. Clinical symptoms were remarkably improved, especially most effective on consciousness level during Fluosol DA-20 infusion and dopamine with Fluosol DA-20. A case using Fluosol DA-20 revealed improvement of clinical symptom without increase of cerebral blood flow. This mechanism is probably related to ability of oxygen content of Fluosol.
Surrounding area of cerebral ischemia showed cerebral blood flow increase with Fluosol DA-20 and/or dopamine infusion, however, ischemic region due to vasospasm did not reveal any increase of blood flow

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The effective therapy for symptomatic vasospasm after subarachnoid hemorrhage was not yet established. We experienced 119 cases of eary operation within 48 hours after subarachnoid hemorrhage in which 44 cases with symptomatic vasospasm belonged in Hunt & Kosnik grade III, IV and same account of cases with symptomatic vasospasm belonged in CT grade IIIa, IIIb. IIIa was indicated that subarachnoid clot was bilaterally thin or unilaterally thick visualized in basal cistern and IIIb was indicated that subarachnoid clot was bilaterally thick visualized in basal cistern.
In these 44 cases we performed control therapy (subarachnoid clot was removed as far as possibly by microsurgical suction-irrigation, cisternal drainage, ventricle drainage if necessary, mannitol, glyceol and steroid) and other therapies using Ca⁺⁺ antagonist (Nifedipine), dopamine, barbiturate (Thiopental), fluoro-carbon (20%Fluosol-DA) and albumin. The effect of these therapies for symptomatic vasospasm were compared with each other and we evaluated the cases in Glasgow Outcome Scale I~III on discharge made good recovery.
The results were as follows.
1) In CT grade IIIa, 7 of 9 cases in control (78%), 5 of 5 cases in Ca⁺⁺ antagonist (100%), 9 of 9 cases in dopamine (100%), 2 of 4 cases in barbiturate (50%), 3 of 3 cases in fluoro-carbon (100%) and 9 of 10 cases in albumin (90%) made good recovery and therapies except for barbiturate showed more effective result than control.
2) In CT grade IIIb, 2 of 6 cases in control (33%), 0 of 2 cases in Ca⁺⁺ antagonist (0%), 3 of 7 cases in dopamine (43%), 0 of 3 cases in barbiturate (0%), 2 of 3 cases in fluoro-carbon (66%) and 2 of 6 cases in albumin (33%) made good recovery and only dopamine and fluoro-carbon showed somewhat effective result.
3) Furthermore, we experienced 3 cases of intracranial hematoma (2 epidural, 1 intracerebral) accompanied with albumin therapy and 2 of 3 cases concluded in poor result.

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It is very important to know the possibility of symptomatic vasospasm after early stage of aneurysm surgery. 162 cases of ruptured aneurysm were operated upon within 3 days after onset in our department. Analysis of comparison of the high density area on the basal cisterns between pre and post operative CT scans of these cases performed. 3 types of the change of pre and post operative CT scans are revealed, namely well removal; almost all high density areas disappeared, slight removal: little high density areas remains, poor removal: less change of high density areas.
Among 162 cases, 40 cases showed symptomatic vasospasm after surgery. Fatal symptomatic vasospasms are 4 cases (3.1%). Correlation between the change of pre and post operative CT findings and symptomatic vasospasm, the cases of poor removal showed symptomatic vasospasm with high frequency and dead cases due to symptomatic vasospasm are in the cases of such poor removal cases.
It is well known the pathogenesis of vasospasm after subarachnoid hemorrhage might be the clots adhered on the main arteries of the brain. Present study suggests it is important to take off such clots during aneurysmal surgery without the damages of vessels and brain tissue to prevent the vasospasm. And it can be also said that when the CT scan after surgery shows thick high density areas on the basal subarachnoid cisterns indicates highly possibility of the occurrence of symptomatic vasospasm.

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An attempt was made to prove clinically one of our contentions, that subarachnoid perivascular acidosis may play a role in the pathogenesis of cerebral vasospasm.
Clinical results of 51 patients treated both with TX synthetase inhibitor to prevent cerebral vasospasm and with pH8.0 Hartmann solution for intracranial irrigation at operation, were compared with those of 82 patients in the previously performed cooperative clinical study of prevention of cerebral vasospasm with OKY-046.
The ratio of patients in the present series operated on during the vasospasm predilection period (4-11th SAH day) was nearly twice that of the OKY-046 study. Incidences of both angiographic and symptomatic vasospasms were definitely lower in the present series. One month after the aneurysmal rupture, the percentage of patients with outcome graded excellent was higher, and the percentage of patients who had died was lower, in the present series.

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Long-term functioning enhanced cisternal drainage was performed, in aneurysmal early stage operation after SAH, to effect continuous wash-out of the subarachnoid blood clot postoperatively.
Thirty-eight patients with Hunt and Kosnik (H & K) clinical Grade I-III who underwent aneurysmal neck clipping within 4 days after SAH were analyzed. Following extensive removal of the cisternal blood clots, the Liliequist's membrane was opened widely to remove clots from the interpeduncular cistern. If sufficient amount of CSF did not come out, third ventriculostomy was effected by making a small hole on the midline of the lamina terminalis. Then, drainage was performed from the carotid cistern. Depending on average amount of drained CSF per-day, drainage effect was divided into poor, moderate and fair groups. Only 2 patients with the enhanced cisternal drainage showed poor drainage effect. SAH was graded into 0-III depending on the amount of cisternal hematoma on admission CT. No symptomatic vasospasm occurred in patients with Grade I of H & K clinical as well as SAH gradings. In patients with Grade II+III of H & K clinical grading, the symptomatic vasospasm occurred in 44, 60 and 36% of patients with poor, moderate and fair drainage effect, respectively. In patients with Grade II+III of the SAH grading the symptomatic vasospasm occurred in 78, 60 and 42% of patients with poor, moderate and fair drainage effect, respectively. Nine patients with symptomatic vasospasm were treated by the hypertensive/hypervolemic therapy (HHT). The HHT was not successful in all 2 patients with poor drainage effect. One year after discharge, patients prognosis was evaluated by the Glasgow Outcome Scale (GOS). Six patients slightly disabled, one severely disabled, another one died. Remaining 30 patients (79%) of“good recovery”were analyzed on the drainage effect depending on the H & K clinical and SAH gradings. The good recovery was found in 63, 100 and 86% of patients with poor, moderate and fair drainage effect in Grade II+III of H & K clinical grading, respectively as well as in 33, 100 and 83% of patients with poor, moderate and fair drainage effect in Grade II+III of SAH grading, respectively.
Thus, the post-operative long-term functioning enhanced cisternal drainage could reduce incidence of vasospasm and gain effect of HHT, and benefit to the outcome of the early aneurysmal operation.

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Although the effectiveness of early operation has been reported for the prevention of symptomatic vasospasm, good results have been obtained only in two-third of the patients, the rest developed neurological manifestations after early operation. The authors have reported that the albumin therapy is more effective for the prevention and the treatment of symptomatic vasospasm than ordinary measures. Based upon this result, the effectiveness of early operation followed by albumin therapy for the severe SAH in order to prevent and treat the later complications of vasospasm were analyzed in this report.
For the last 4 years, 45 patients with severe SAH as classified to the Group 3 after Fisher, were operated within 4 days after the onset and were followed by albumin therapy prophilactily. Numbers of their grade (after Hunt & Kosnik), grade 1 & 2, 3, 4, 5 were as follows; 17, 17, 10, 1 respectively. Operative procedure was carried out by the trans-sylvian approach (32 cases) or trans-interhemispheric approach (13 cases). After the operation, albumin therapy was begun with the initial dose of 1.0g/kg/day. In case that neurological manifestation developed, the dose of albumin was increased to 1.5-2.5g/kg/day.
7 died and the morbidity rates of good recovery, moderately disabled, severely disabled and persistent vegetative state (after Glasgow Outcome Scale) were as follows; 33/45 (69.8%), 2/45 (4.4%), 3/45 (6.7%) and 2/45 (4.4%) respectively. The result for the prevention of symptomatic vasospasm with the initial dose of albumin administration, only 5 patients (11.1%) out of 45 developed symptomatic vasospasm. Among these 5 patients, 3 patients recovered completely, only 2 patients (4.4%) were resisted to this measures.
It could be said that this measure is the most valuable for prevention and treatment of symptomatic vasospasm in patients with severe SAH.

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Delayed cerebral ischemia following severe subarachnoid hemorrhage is difficult to prevent or treat in those not treated by surgery early after the onset. We examined the effectiveness as well as limitations of albumin therapy in the prophylaxis and treatment of delayed cerebral ischemia.
We studied 47 patients with severe subarachnoid hemorrhage classified as Group 3 by Fisher's CT grading encountered during the past 4 years who received albumin therapy but did not undergo early surgery for various reasons. The patients consisted of 22 males and 25 females ranging in age from 28-76 years (mean, 52.7 years). On the initial examination, 8 patients were classified as Grade I or II by the scale of Hunt & Kosnik, 6 as Grade III, 14 as Grade IV, and 19 as Grade V. The site of the aneurysm was in the anterior cerebral artery in 19 patients, middle cerebral artery in 8, internal carotid artery in 10, vertebral-basilar system in 2, and indeterminate in 8. The dose of albumin was 1.0g/kg/day prophylactically, but was increased to 1.5-3.0g/kg/day with the appearance of symptomatic vasospasm. The hypertensive tendency was controlled with various hypotensive agents.
Eleven of the patients showed good recovery, 6 were moderately disabled, 3 were severely disabled, 3 exhibited vegetative states, and 21 died. Of the 18 patients operated on, 11 showed good recovery, 4 were moderately disabled, 3 were severely disabled, but none showed a vegetative state or died. Symptomatic vasospasm occurred in 20 patients (42.6%), but the albumin therapy was ineffective in only 5 patients. Twenty-one patients died before surgery, 14 of them due to rerupture, 3 due to vasospasm, 2 due to sepsis or DIC, and 2 due to cerebral edema complicated or uncomplicated by spasm.
Although delayed cerebral vasospasm occurred after severe subarachnoid hemorrhage in 42.6% of the patients not undergoing early surgery, it was refractory to increased albumin doses in only 5 patients, suggesting the effectiveness of the therapy. Patients in whom increases is blood pressure could not be managed with hypotensive agents often suffered from rerupture and were associated with poor outcomes.

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Purpose: To examine the problems concerning surgery for ruptured cerebral aneurysm in the acute phase, patients who were surgically treated on Day 0-Day 2 of the rupture and had unfavorable outcomes were divided into those receiving and not receiving albumin therapy, and factors affecting the prognosis were studied in each group.
Subjects and Methods: Radical treatment of cerebral aneurysm was conducted on Day 0-Day 2 of the occurrence of subarachnoid hemorrhage in 105 patients by 10 surgeons. Those preoperatively showing Hunt & Kosnik grades of I -III (grades not adjusted upward due to circumstantial factors) were divided into those who had received (61 patients) and not received (22 patients) albumin therapy. Twenty of these patients who became severely disabled, showed a vegetative state, or died were then classified according to the factors that were primarily responsible for the outcome: operative insult (OP), operative insult and vasospasm (OP+ VS), vasospasm (VS), and others.
Results: The outcome was unfavorable in 8 (36%) of the 22 patients not treated by albumin therapy, of whom 6 (27%) died. The factors responsible for the outcome were OP in 3 (14%), OP+VS in 3 (14%; treated with isoproterenol), and VS in 2 (9%; 1 treated with isoproterenol and 1 by stellate ganglion blocking). Twelve of the 61 patients treated by albumin therapy showed un-favorable outcomes, and 8 of them died. The factors responsible for the outcome were OP in 8 (13%), OP+VS in 2 (3%), VS in 0, and others in 2 (3%; fulminant hepatitis in 1 and OP+renal failure in 1).
Conclusion: Operative insult and vasospasm accounted for 28% and 23%, respectively, of the causes of the poor outcome in those not treated with albumin. By contrast, operative insult was involved in 18% and vasospasm only in 3% of those treated with albumin, suggesting the effectiveness of albumin therapy.

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Serial measurements of CBF using ¹³³Xe inhalation technique and cerebral oxygen metabolism were carried out in patients who were treated postoperatively with hypervolemic hemodilution therapy. Patients with cerebral vasaspasm showed significant reduction of CBF and cerebral delivery of oxygen (D-O₂) and an elevation of oxygen extraction fraction (OEF). Significant reductions of cerebral metebolic rate of oxygen (CMRO₂) were not observed in patients with non-symptomatic vasospasm due to the elevation of OEF. In patients with symptomatic vasospasm, marked reductions of D-O₂ were followed by significant reductions of CMRO₂ in spite of the elevation of OEF. A critical CBF level of about 25ml/100g/min (45% of normal value) was noted in patients who developed neurological symptoms with LDAs on CT scan.
Influence of hematocrit (Ht) values on D-0₂ was evaluated in 24 cases including 4 patients with cerebral ischemic attack due to cerebral vasospasm, and optimal Ht value (X) and maximal D-O2₂ (Y) were calculated in each cases. There was a close correlation between X values and Y values (r=0.91). This data suggest that D-O2₂ in normal subjects becomes maximum in condition of a Ht value of about 40-45%, however, when D-O2₂ reduces in a half value of normal condition in patients with cerebral vasospasm and cerebral ischemia, maximal D-O2₂ is expected in condition of a Ht value of about 27-30% (Hemodilution).
These results indicate that hypervolemic hemodilution therapy improves only cerebral perfusion but cerebral oxygenation during the period of cerebral vasospasm.

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Hypervolemic hemorheological therapy for cerebral vasospasm were evaluated in 46 cases operated within 72 hours after subarachnoid hemorrhage. Subjects were divided into 2 groups: the cases of mild hypoperfusion (CBF more than 35.1cc/100g/min), and those of severe hypoperfusion (CBF less than 35.1). In those of mild hypoperfusion, CBF showed negative correlation with Ht. The interrelationship between oxygen delivery and Ht showed optimal Ht between 35 and 40%. In those of severe hypoperfusion, Ht could exert less influence upon cerebral circulation and metabolism than in those of mild hypoperfusion, suggesting a limitation of hemodilutional therapy for severe vaso-spasm. Hypervolemic hemorheological therapy maintaining 35-40% of Ht and 10-12cm H₂O of CVP was considered to be effective from the viewpoint of clinical outcome and that of cerebral circulation.

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Plasma volume, central venous pressure and water balance of 24 patients were measured about first and second week after early operation for the ruptured aneurysms. All of the patients had been treated by induced hypertension therapy for delayed vasospasm successfully. Plasma volume was measured by RI method using RISA.
The average of plasma volume of 16 patients was 58.3±6.0ml/kg. This group had 200ml of 25% albumin every day. It was 48.2±6.2ml/kg on 8 patients without albumin. The average of CVP was 11.3±2.2cm on the albumin group. It was 5.3±1.5cm on the other group. The value of plasma volume and CVP was higher statistically on the albumin group than the other group. Water balance was positive on about half of the albumin group. It was negative on the other group. 3 patients of the albumin group had pulmonary edema.
The conclusion: 1 The state of patient's hydration is not hypovolemic, as far as the induced hypertension therapy is possible, even though patient's CVP is low and water balance is negative. 2 Albumin lets the plasma volume increase easily. Therefore, the risk of pulmonary edema may rise when only unreliable CVP is used for the monitoring of plasma volume. 3 Plasma volume measurement is indispensable to the monitoring of fluid management for vasospasm and plasma volume should be aimed at 55-60 ml/kg.

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Symptomatic vasospasm (SVS) is an important factor that determines the outcome of patients undergoing early surgical intervention for ruptured aneurysm. We have been dealing with patients who showed SVS progressing despite of mild hypervolemic and/or hypertensive therapy by placing them on further aggressive hyperdynamic therapy using systemic vasodilator which is expected to dilate capacitance vessels. Twenty-five consecutive cases out of 161 patients undergoing early operation within 48 hours after aneurysmal rupture were studied and showed significantly better outcome than that of control group especially as to those at lower (IIIb+IV) grade preoperatively.
Changes of cardiac output (CO) and circulating blood volume (CBV) were studied to know the provisional goal of this aggressive therapy. Forty-five% increase of CO and 18% of CBV were found to give a satisfactory result. These figures, 45% of CO and 18% of CBV, were just the average increase rate of those two parameters of 25 cases studied, and thought to be obtainable easily and safely.

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Combination therapy of (1) hypervolemia with albumin, (2) artificial blood substitute (Fluosol-DA 20%) and (3) induced hypertension was performed for the treatment of symptomatic vasospasm. Outcome was compared between thus treated patients (Treated group) and those without the specific treatment ( Non-treated group) in (1) 27 patients undergoing early operation whose subarachnoid hemorrhage (SAH) was in group 2 according to Fisher's classification and (2) 27 patients undergoing early operation whose SAH was in group 3.
Vasospasm appears at a low rate of 22% as well as in mild degree in Fisher group-2 regardless of the treatment, which contributes to the satisfactory result observed in this group (Table 1).
The outcome of the treated group in Fisher group-3 is proved to be fairly good with“Excellent”and“Good”patient rate of 64%(Table 2), which seems largely to be attributed to the prophylactic effect of hypervolemia on vasospasm.
60% of the patients in Hunt & Kosnik grade IV, 39% in grade III, and 13% in grade I and II fall into unfortunate outcome (Fair, Poor, Dead). These results seem to be ascribed to initial impact of SAH, vasospasm and following hemorrhagic infarction, and intracranial hemorrhage due to hemorrhagic diathesis. Attention must be given to fluctuation of systemic blood pressure and hemorrhagic diathesis even in the 3rd week after SAH.

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The authors analyzed 147 cerebral angiograms of 56 cases with ruptured aneurysms which were operated on within 3 days after SAH and showed vasospasm postoperatively. Characteristics of postoperative vasospasm and the correlation between vasospasm, and patients' prognosis, cerebral blood flow and infarction on CT scan were examined. Up to now, we have used the type of vasospasm after Saito in which angiographical findings were morphologically classified. In this study, we have tried a quantitative measurement of the extention and degree of vasospasm.
The results were as follows: 1) Compared with preoperative vasospasm, postoperative vasospasm occurred in more distal branches of cerebral arteries, namely, in M 2-3 portion of the middle cerebral artery or A 2-3 portion of the anterior cerebral artery. This may be mainly due to the fact that the cisternal clots near the proximal portion of cerebral arteries could be removed by early operation and continuous cisternal irrigation postoperatively. 2) Distal and extensive type of vasospasm exerted more crucial influences upon patients' prognosis, CBF and formation of cerebral infarction than proximal type of postoperative vasospasm.
Quantitative estimation of vasospasm was not yet satisfactory and its technical limits and methodological aspects were also disussed.

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Seven hundred and seven carotid angiograms of 305 patients with ruptured intracranial aneurysms were analyzed to investigate the sequential changes of the type and severity of vasospasm. Furthermore, the study was undertaken to analyze the effect of vasospasm upon clinical states, cerebral circulation, the development of cerebral infarction and prognosis of the patients.
Vasospasms were simply classified according to their extents into four types; diffuse (narrowing intraarterial diameter over 2cm in length in the proximal parts), peripheral (narrowing over 2cm in length in the distal parts), multi-local and local. The diffuse type of vasospasm was further divided into two grades of severity; diffuse severe (reduction of the caliber by more than 50%) and diffuse mild (reduction of the caliber by 25 to 50%). Measurements of the rCBF were undertaken by the intra-arterial Xe-133 injection method.
The results were as follows: 1) Vasospasm which occurred within 3 days after the onset was seen in only 3 of 79 cases. However, the incidence of vasospasm increased as time passed and reached its peak at the period between 8th and 15th day, when vasospasm was seen in 83 of 106 cases. The type of narrowing was diffuse in most of these cases. Thereafter, the occurrence of vasospasm gradually decreased and the type of narrowing tended to change from diffuse to local or multi-local types. Only a few cases showed vasospasm after 50th day. 2) Most of the patients with the diffuse type of vasospasm, especially with the diffuse severe type, showed decreases of mean CBF, while mean CBF of the patients with the multi-local or the local type of vasospasm showed no meaningful decrease when compared with the patients without vasospasms. 3) Twenty out of 38 patients with the diffuse type of vasospasm developed cerebral infarctions, while none of the 14 patients with no vasospasm or the local and multi-local types of vasospasm developed cerebral infarctions. 4) The diffuse type of vasospasm tended to have some effects on the clinical state and outcome of the patients.
It was concluded that the present method of classifying the degree of vasospasms was useful in determining a clinical significance of vasospasms.

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Up to now, it has been accepted that subarachnoid blood and/or products play an important role in cerebral vasospasm after aneurysmal subarachnoid hemorrhage.
The purpose of this study is to evaluate clot volume of subarachnoid hemorrhage by CT scans as exactly as possible. On a CT scan, if the total subarachnoid blood is considered as a mass (=volume x density), the amount is calculated as a clot score (=cts) which consists of the thickness, density (CT number) and localization, i. e. cts's in our method were measured on six cisterns and four points fissures, and one cistern or one fissure was given respectively one to three points in proportion to the degree of density and thickness as measured by CT scan. Total maximum cts points were thirty.
Conversely, cerebral vasospasm has been assessed and graded by angiography, based on the reduction rate in the caliber of the major arteries.
During the past 6 years, 68 of 271 patients with aneurysmal subarachnoid hemorrhage who had undergone serial CT scan and angiography after the ictus, were made available for this study.
Among these cases, the cts was compared with the incidence of angiographic vasospasm and the effects by various treatments against cerebral vasospasm.
Also, in five cases, RI cisternography was performed by means of lumbar puncture from Day 3 to 8 and cerebro-spinal fluid (CSF) dynamics were examined.
Consequently, 1 ) our method resulted in a good correlation between the amount of blood and the severity of angiographic vasospasm in spite of both early and delayed surgery for ruptured aneurysms, 2) in the early stage after aneurysmal subarachnoid hemorrhage, CSF seldom circulated smoothly, and 3) continuous cisternal drainage (CCD) was the most effective treatment of all against cerebral vasospasm.
It was suggested that applying cts to the parameter of a cerebral vasospasm, early surgery with extensive removal of the hematoma, and then, CCD in abnormal CSF dynamics were effective in preventing cerebral vasospasm.

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The relationship between the amount and distribution of subarachnoid clots visualized on pre- and postoperative CT scans and the incidence of symptomatic vasospasm (SVS) was studied in 61 cases of ruptured aneurysms who were operated on within 3 days of subarachnoid hemorrhage. Changes in the amount of subarachnoid clots by the surgery with a cisternal drainage were also examined.
The operation was performed through a pterional approach as a rule, and subarachnoid clots were removed as much as possible around the aneurysm and from the basal cisterns of operated side. A thin silicon catheter was introduced into the prepontine cistern after opening Liliequist membrane, and bloody cerebrospinal fluid was continuously drained through the catheter for at least a week after the surgery. Postoperative CT scans were taken within 24 hours of the operation. The amount of subarachnoid blood was estimated on CT scans in the basal frontal interhemispheric fissure (IHF), the suprasellar cisterns, the stem of Sylvian fissures, and the insular cisterns. They were classified into 3 degrees as hypodense, mild high, and markedly high.
Twenty cases (33%) developed SVS which was the cause of bad outcome in 9 cases (permanent spasm) and signs and symptoms of SVS had improved with time in 11 cases (reversible spasm). On the study of the distribution of subarachnoid clots, 10 of 16 cases (64%) with markedly high in the cisterns embedding both the anterior cerebral artery and the middle cerebral artery developed SVS ( 6 permanent and 4 reversible), while 7 of 22 cases (32%) with markedly high in the cisterns embedding either of the two arteries developed SVS (3 permanent and 4 reversible). Among 23 cases without markedly high, 3 cases (16%) developed reversible SVS. By the early operation associated with a cisternal drainage, the amount of subarachnoid clots was significantly reduced from markedly high to mild high or hypodense in over 70% of the suprasellar cisterns and the stem of sylvian fissures, but in 44% of the basal frontal IHF and in 27% of the insular cisterns.
It is concluded that postoperative CT scans were useful in predicting patients in jeopardy of developing SVS in cases of ruptured intracranial aneurysms with an early operation.

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Table 1 shows 239 cases of ruptured intracranial aneurysm which admitted to the Iwate Prefectural Central Hospital.
CT findings were graded from I to V as follows (Fig. 1), Grade I: No abnormality or isodensity in CT findings. Grade II: High density area only in the cistern in which the ruptured intracranial aneurysm exists. Grade III: High density areas also in cisterns other than that in which the ruptured intracranial aneurysm exists. Grade IV: Symmetrical extremely high density areas in all cisterns. Grade V: Presence of massive intracerebral or intraventricular haematomas.
With respect to distribution of ruptured cerebral aneurysms and CT findings, comparisons were then made of the morbidity and mortality rates between the 115 cases (Group A) operated on within 3 days of SAH and 72 cases (Group B) operated on 4 or more days afterwards.
The mortality rate was 13.9% in Group A and 2.7% in Group B. The morbidity rate was 22.6% in Group A and 30.5% in Group B (Table 2,3).
Among the 52 fatal cases not operated on, 11 patients died from rebleeding while waiting for operation and 6 from vasospasm, which would have been Grade II-III according to Hunt-Kosnik's criteria, the patients lives were saved because of operations being performed within 3 days. Combining these cases, the mortality rate for those waiting for operations was 21.3%. The remaining 35 of these 52 fatal cases were inoperable with Grade V of Hunt-Kosnik.
Correlation between CT findings and Grading of Hunt and Kosnik shows that death from postoperative vasospasms and brain edemas occurred in ten of 31 cases with Grade IV of CT finding. All these ten cases would have been classified as Grade II or III according to Hunt and Kosnik's criteria in early surgery (Table 4). So, grading based on CT findings are more useful in predicting postoperative results than Hunt and Kosnik's gradings.

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We have proposed an ultra-early operation for ruptured intracranial aneurysms and emphasized the importance of removing subarachnoid clot existing around the brain artery, which may play a major role in producing vasospasm. In the present study, we investigated the correlation between CT findings of subarachnoid hemorrhage before and after operation and the post-operative incidence of cerebral vasospasm in patients undergoing an ultra-early operation for ruptured intracranial aneurysms.
The investigation was performed in 53 patients, among the 166 patients who underwent an operation for ruptured intracranial aneurysm in our division during the 2-year period from January, 1982 to December, 1983, on whom the operation was performed within 48 hours after the last episode. First CT findings of subarachnoid hemorrhage (SAH) were classified by modifying the classifications of Suzuki et al. and Fisher et al. into 4 degree with reference to the distribution and volume and Hounsfield number.
Of the 53 cases, none was classified into Grade I preoperatively, with 9 belonging to Grade II, 22 to Grade III and 22 to Grade IV. Cerebral vasospasm developed in 1 case of Grade II (11%), 3 of Grade III (14%) and 10 of Grade IV (41%). Whereas in the CT performed within 24 hours after operation, 37 cases showed an improvement of one CT grade or more and 16 cases showed no change. Cerebral vasospasm developed in 6 of the former cases (16%), but in 8 of the latter cases (50%). Thus, a high correlation was found between the preoperative CT grade and the onset of cerebral vasospasm.
This investigation suggests that even if the preoperative CT grade is high, the development of cerebral vasospasm may be prevented by removing the subarachnoid clot as much as possible.

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The relationship between cisternal high density calculated by Hounsfield-number (HN) in computed tomography and subsequent development of cerebral infarction due to delayed vasospasm (VS) was studied retrospectively in 36 cases with ruptured cerebral aneurysm. All patients were hospitalized within 24 hours and operated within 48 hours after subarachnoid hemorrhage. Extensive removal of cisternal blood clots were carried out after obliteration of the aneurysm.
The relation between HN in post-operative CT and VS was noted as follows. When HN was less than 68, VS did not occur in any of the cases. When HN was ranged from 68 to 73, the incidence of VS was 50%. When HN was 73 or more, VS occurred in all of the cases.
In view of these results, a new grading according to HN for the incidence of VS was proposed, that is, no cisternal high density=grade I, HN of less than 68 = grade II, HN ranged from 68 to 73=grade III, HN ranged from 73 to 78=grade IV, and HN of 78 or more = grade V. This grading was very useful to decide the timing of operation and to determine the sites and degree of clots to be removed.
In comparison with HN grading to Fisher's classification, the HN grade II mainly corresponded to Fisher's class II, and Fisher's class III corresponded to HN grade III to V. Thus, the HN grading was not only very precise and quantitative but it serves the purpose for prediction and protection of highly VS prone patients.

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Multifactorial analyses were performed on patients with early surgery (within 72 hours) for ruptured intracranial aneurysms (Hunt gr I-IV) with respect to their CT findings and prognosis. There were 68 cases of internal carotid (ICA), 65 anterior communicating (ACoA), and 53 middle cerebral (MCA) aneurysm. Over all good prognosis (Glasgow Outcome Scale: 1-2, at 6 months) was obtained in 70% of all patients. The main findings are listed as follows:
1) Thick subarachnoid clot (>1mm) in quadrigeminal cistern was accompanied by high mortality rate of over 50% in ICA and MCA, while it reached 75% in ACoA.
2) Delayed angiographic vasospasm was seen in 65% (ICA), 62% (MCA) and 39% (ACoA) of patients with thick SAH on CT.
3) Shunt operations were necessary in 12% (ICA and MCA) and 25% (ACoA) of patients. However these values rose to 21% (ICA), 36% (MCA) and 42% (ACoA) when acute hydrocephalus (CV Index>15%) was noted on preoperative CT.

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Three dimentional analyses of local cerebral blood flow (ICBF) and pool (ICBP) were done in 26 patients with ruptured intracranial aneurysms. The sites of the aneurysms were as follows: 4 in the internal carotid, 12 in the anterior communicating, 8 in the middle cerebral, and two in the vertebral arteries. The serial changes of ICBF, ICBP under various pathophysiological conditions were analyzed. LCBF was obtained by ¹³³Xe inhalation method and ICBF by ^99mTc-HSA (human serum albumin) injection method.
The results were as follows:
1) Reduction of ICBF and uptake of ^99mTc-HSA produced by surgical procedures were localized and recovered in a few weeks.
2) Mild reduction (20-30%) of ICBF in general was recognized even in the patients without vasospasm postoperatively.
3) Only mild reduction of ICBF without uptake of ^99mTc-HSA showed good prognosis for the patients.
4) Severe reduction of ICBF with high uptake of ^99mTc-HSA in the acute phase showed poor prognosis for the patients. And they often associated with global cerebral infarction or hemorrhagic infarction in the subacute phase.
5) SPECT study under induced hypertention treatment with dopamine HCI infusion in the patients with vasospasm revealed heterogeneously disturbed areas of autoregulation of the cerebral blood flow depending on cases and sites of the lesion.
Three dimentional analyses of local cerebral blood flow and pool were useful to detect the pathophysiology after ruptured intracranial aneurysm and to deside the adequate therapy for patients.

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Regional cerebral blood flow (rCBF) was estimated by the Xe¹³³ venous method in 37 preoperative patients with subarachnoid hemorrhage (SAH) due to rupture of a cerebral aneurysm. Daily estimates were made during first about 2 weeks after SAH (98 studies). The rCBF fell progressively with various degrees during the first 2 weeks after SAH. The marked reduction of rCBF was observed in the group of old age, hydrocephalus, severe SAH on CT scan and ruptured anterior communicating aneurysm. However, there was no significant difference of rCBF in the grade of Hunt and Hess on admission, this reason was thought not to be estimated rCBF in the grade IV and V of Hunt and Hess for the death in their way. Twenty-four of the patients were taking inhibitor of thromboxane A₂ synthetase (OKY-046) for preventing of cerebral aneurysm, other 13 patients were not taking. The reduction of rCBF in the group treated with OKY-046 tend to be suppressed, comparing to it in the group with no treatment. And OKY-046 prevented the decreasing of rCBF significantly at 2 weeks after SAH.

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