To investigate the possibility of predicting cerebral ischemia due to cerebral vasospasm in subarachnoid hemorrhage (SAH), serial evaluation of the cerebral vasodilatory capacity by the acetazolamide test was conducted, using single photon emission computed tomography (SPECT) and N-isopropyl ¹²³I-p-iodoamphetamine (IMP), in 17 patients with cerebral vasospasm following early surgery for ruptured aneurysms. The degree of vasospasm measured on the angiograms was classified into the following three types: mild degree (25%>stenosis), moderate degree (25-50% stenosis), and severe degree (50%<stenosis). In four patients with asymptomatic vasospasm (mild degree), the cerebral vasodilatory capacity was preserved at the normal level during the period of vasospasm. In eight patients with asymptomatic vasospasm (moderate degree), a trasient limitation of cerebral vasodiratory capacity was observed between the 6th and 16th day after a rupture of the cerebral aneurysm. In five patients with symptomatic vasospasm resulting in reversible ischemia, a marked limitation of cerebral vasodilatory capacity was noted between the 7th and 15th day, and a delayed recovery of cerebral vasodilatory capacity was observed. This reversibilty of cerebral vasodilatory capacity in patients with cerebral vasospasm suggests that a local decrease of purfusion pressure due to cerebral vasospasm causes compensatory vasodilation of intraparenchymal arteries and the vasodilatory reaction to acetazolamide was limited until the release of the cerebral vasospasm. Therefore, assessment of cerebral vasodilatory capacity in SAH by the acetazolamide test might predict the appearance and continuation of potential ischemia of the brain caused by the reduction of perfusion pressure due to cerebral vasospasm.
The mechanisms of cerebral vasodilatory reaction to the acetazolamide are discussed in this paper.

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Noninvasive diagnostic methods of transcranial Doppler (TCD) sonography and single photon ECT (SPECT) were used for predicting vasospasm in 41 cases with ruptured cerebral aneurysm in the acute stage. The degree of vasospasm in the M₁ segment of the affected middle cerebral artery (MCA) was evaluated according to Fisher's classification on angiograms conducted between seven and 11 days after the last attack. Mean flow velocity in the affected M1 segment was serially measured by TCD during the 14 days after the last attack in 24 cases. CBF was measured by SPECT with Xe-133 inhalation between seven and 13 days after the last attack in 26 cases. Mean CBF was calculated in the affected MCA region.
Four cases with no vasospasm in the M₁ segment on the angiogram showed no alteration in mean flow velocity for the same segment. Nine cases with slight to moderate vasospasm on the angiogram included six cases which revealed a mild increase in mean velocity, and three cases which showed no change. Of 11 cases with severe vasospasm demonstrated angiographically, three cases showed a marked increase in mean velocity; a mild increase was recognized in seven cases; and one case showed no change. On the contrary, there was no apparent difference in the change of mean flow velocity between cases with or without neurological deterioration due to vasospasm. Mean CBF value for the affected MCA region in the cases with severe vasospasm on the angiogram was slightly lower than the value for those who were not affected severely. However, mean CBF value in the cases with neurological deterioration due to vasospasm was markedly lower than that without the deterioration.
The above results suggest that the changes in flow velocity in the M₁ segment measured by TCD show the severity of vasospasm on the angiogram. On the other hand, mean CBF value measured by SPECT would be a useful indicator of subsequent neurological deterioration following the vasospasm rather than of the evaluation of vasospasm demonstrated on the angiogram. Therefore, noninvasive prediction of vasospasm and subsequent neurological deterioration using TCD and SPECT would be useful in elucidating the pathophysiology and the course of treatment of vasospasm.

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Flow velocities of the middle cerebral artery were monitored with a transcranial Doppler TC2-64 in 33 patients with a proven subarachnoid hemorrhage (SAH) due to ruptured aneurysms. Eleven of the aneurysms were located on the posterior communicating artery, nine on the middle cerebral artery, ten on the anterior communicating artery, one on the vertebral artery, and two were of unknown origin.
Maximum flow velocities were encountered on day 10 to 20. In ten patients discharged without neurological deficits, five showed reversible delayed ischemic neurological symptoms with maximum flow velocities faster than 150cm/sec whereas five showed no ischemic deficit with maximum flow velocities slower than 100cm/sec. Three to four weeks after SAH flow velocities returned to normal in all cases in this group. In 23 patients discharged with neurological deficit due to vasospasm, maximum flow velocities registered were faster than 150 cm/sec in ten, 100-150cm/sec in eleven, and less than 100cm/sec in two. Flow velocites of this group of patients remained higher than normal even three to four weeks after SAH. However, flow velocities of four patients who eventually deteriorated to a vegetative state decreased to less than normal.
In order to detect the influence of intracranial pressure on the spastic arteries on the Doppler sonagram, a single arterial velocity wave was analyzed by fast Fourier transform (FFT) using a minicomputer. The frequencies with maximum power in the peak systolic (HFpp) and in the end-diastolic phase (LFpp) were extracted. Preliminary results revealed that in patients with SAH both HFpp and LFpp decreased with a rising ICP.

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In the pathogenesis of symptomatic vasospasm after subarachnoid hemorrhage (SAH), hyperactivity of the platelet, hypercoagulable state and impairment of cerebral microcirculation are considered to play important roles. The authors assess the incidence and clinical course fo symptomatic vasospasm in 88 aneurysmal patients with a uniform management protocol of antiplatelet, Ca blocking agent, and hypervolemic therapy. All patients received an antiplatelet agent (Ticlopidine) and a Ca blocking agent (Nicardipine) after surgery was performed within 48 hours following SAH. The flow velocity of the middle cerebral artery (MCA. FV) was measured after surgery by transcranial Doppler sonography (TCD), and when MCA. FV exceeded 120 cm/sec within seven days after SAH, hypervolemic therapy was started with albumin and Hetastarch. Nine patients (10%) developed characteristic signs and symptoms of symptomatic vasospasm in spite of these managements, but major neurological deficits from vasospasm occurred only in three patients (3%). In the total series, 70 patients (80%) had a good outcome and only five patients (5.7%) died of cardiac, pulmonary complication or sepsis. There were no fatal complications attributable to the antiplatelet agent, Ca^? blocking agent or hypervolemic therapy.
This management strategy may lower the incidence of death and disability from vasospasm after SAH.

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Subarachnoid hematoma has been removed surgically for prevention of vasospasm, especially in cases of severe subarachnoid hemorrhage (SAH). In this study, surgery for ruptured aneurysms with severe SAH was performed at the early stage in 106 cases. The degree of SAH was classified into three grades (0-2 points) according to Fisher's CT grade in each of the eight cisterns. The SAH score was calculated by integrating the CT grade in all cisterns, and patients with an SAH score of more than nine points were defined as having severe SAH. The thick clot was actively removed after the clipping of the aneurysm through a unilateral craniotomy (scavenger surgery) in 77 operations performed by several neurosurgeons, and in the residual 29 cases the clot was not removed or was removed only around the ruptured aneurysm (conventional surgery). The outcome of hematoma removal in the scavenger surgery was analyzed and compared with that in the conventional surgery by calculating the percent of residual SAH (post-operative SAH score/ pre-operative SAH score). The residual SAH was 36% in the scavenger surgery, and 54% in the conventional surgery. The point was calculated also in each part of the cistern. By the scavenger surgery, the amount of SAH was markedly reduced to lower than 30% in both sides of the carotid cistern and of the sylvian cistern, while the marked reduction was limited to the carotid cistern of the craniotomy side by the conventional surgery. But even by the scavenger surgery, surgical clearance was not sufficient in the interhemispheric cistern or in both sides of the insular cistern, and the residual SAH was more than 50%. This suggests that scavenger surgery reduces the total amount of SAH, but it is not enough to prevent vasospasm of the A₂ and M₂ portion. It shows the limitation of surgical clearance by the scavenger surgery.

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The incidence of cerebral vasospasm and results were analized in 257 patients with high scored SAH (Fisher's Group 3) in a multicenter study. Patients were divided into three groups according to surgical principles: “conventional surgery” in the acute stage, “scavenger surgery” (active subarachnoid clot removal) and “delayed surgery” (wait until the later stage). A subgroup analysis was made on cerebrospinal fluid drainage and on irrigation with urokinase. Symptomatic vasospasm was the lowest in the “scavenger surgery” group with a statistical difference (p<0.01) between it and the“conventional surgery”.
Severe cerebral infarction was decreased by active clot removal. The excellent result increased from 39% to 54% by clot removal in the acute stage. Postsurgical CSF drainage or irrigation with urokinase was effective when they were combined with “scavenger surgery”, but not with “conventional surgery”. Surgical complication caused by clot removal was only 5.4%. In the “delayed surgery” group, more than 60% of the patients died without the chance for surgery. It was concluded that active subarachnoid clot removal with postsurgical drainage or irrigation could offer a remarkable improvement of results by its prophylactic effect on vasospasm in patients with severe subarachnoid hemorrhage.

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In order to evaluate the usefullness on cisternal irrigation with urokinase (UK) for severe subarachnoid hemorrhage after aneurysm surgery, we defined the “CT score” and select a group of patients designated “Full Packed SAH” who had a CT score of more than eight points. All 22 patients had diffuse thick subarachnoid clots and the mean Hounsfield number of each cistern was 63.92. Early operation (within 48 hours), removal of subarachnoid clots and subsequently UK irrigation for one week were conducted in most of the cases. The use of spinal drainage and intermittent irrigation with UK were useful for efficient clot removal and maintenance of irrigation. Permanent disability or death occured in nine cases (41%) in whom UK irrigation was performed (in particular, symptomatic vasospasm occured in 23%), against 61% in whom UK irrigation was not done. Seven cases died from vasospasm (3 cases), meningitis, other aneurysm rupture, pneumonia, and aneurysm rupture in anesthesia.
In conclusion, we evaluate the usefullness of early operation, removal of subarachnoid clots and cisternal irrigation with UK for diffuse severe subarachnoid hemorrhage (“Full Packed SAH”) after aneurysm rupture.

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We analyzed the efficacy of cisternal irrigation therapy by Urokinase (UKI) in cases with severe subarachnoid hemorrhage.
Forty-two patients with ruptured aneurysms were operated on within 24 hours after subarachnoid hemorrhage. The clinical grading (Hunt & Kosnik) was III to IV in this series, and the CT grading (Fisher classification) was III to IV excluding cases with parenchymal hematoma.
All patients were treated with hemodilution & normo-hypervolemic therapy postoperatively. Twenty-five were treated with UKI, and seventeen without UKI. There were complications in three patients treated with UKI, and UKI was stepped in mid course.
In fourteen (63.3%) of the patients treated with UKI, CT showed that perimesencephalic cisternal clots were dissolved within three days after subarachnoid hemorrhage (A-group). In the other eight patients, the cisternal clots were dissolved within seven days (B-group). But insular cisternal clots tended to remain in spite of UKI.
Symptomatic vapsospasm was recognized in 50% of the A-group, 75% of the B-group, and 94.1% of patients treated without UKI. Among the A-group, especially in H & K grade III, symptomatic vasospasm was minimal if it was recoginized clinically.
There was no significant differences between the patients of B-group and patients without UKI, especially in H & K grade IV. The duration of UKI treatment was not correlated to the rate of symptomatic vasospasm.
On the Glasgow Outcome Scale, the rate of good and moderate disability was 71.4% of A-group, 50.0% of the B-group, and 47.1% of the group untreated with UKI.
We consider that UKI is beneficial in the prevention of symptomatic vasospasm, and that it is important and contributory factor in preventing the development of delayed ischemia to dissolve and reduce subarachnoid clots within three days.

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In this paper, the treatment of patients with severe aneurysmal subarachnoid hemorrhage of Fisher's classification III alone is persented, applying acute surgery and pharmacological prevention of symptomatic vasospasm.
Calcium-antagonist flunarizine is administered orally from just after early operation until 22 days after subarachnoid hemorrhage.
The results in a series of 16 patients showed no permanent ischemic neurologic deficits from delayed vasospasm: on the other hand, the same number of patients who were not treated by flunarizine showed six permanent ischemic neurologic deficits including three deaths due to delayed vasospasm. There were no side effects from flunarizine.
From this evidence, it might be concluded that flunarizine significantly inhibits the occurrence of severe neurological deficits due to delayed vasospasm. This highly benefical effect might be attributable to its intense inhibitory action on cellular Ca²⁺ overload.

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Prevention of delated ischemic neurological deficits (DIND) following subarachnoid hemorrhage (SAH) has been tried by the surgical removal of subarachnoid hematoma as much as possible during the operation and continuous drainage of the cerebral ventricle and cistern postoperatively. Concomitant pharmacotherapies with administration of mannitol, glyceol, steroid, nizophenon, low-molecular dextran, barbital, Ca⁺⁺ antagonists, or antithrombocyte agents as well as management of Hypervolemia and Hypertension have been used and the clinical outcome is generally improving. In spite of the above treatments, however, prognosis is still infavorable in some cases. Delayed vasospasm is thought to be caused by an angiospastic substance produced in the course of decomposition of the shed blood. We administered urinastatin and gebaxate medilate, polyvalent anti-enzymatic agents, immediately after SAH and our clinical observation has led to the impression that the treatment could prevent DIND in the patients.

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Four hundred seventy-one patients with subarachnoid hemorrhage due to ruptured intracranial aneurysms were admitted between January 1982 and November 1987. Of these, 168 (35.7%) were clinically severe and were classified as Hunt and Kosnik Grade III and IV. In these patients, the results of early radical operation for ruptured intracranial aneurysms with postoperative calcium antagonist and/or anti-platlet drug were examined with regards to the occurrence of cerebral vasospasm and outcome of patients. Early operation increased the number of good cases in outcomes and slightly reduced the incidence of symptomatic vasospasm. Calcium antagonist and antiplatelet drug administered immediately after operation increased the number of good outcomes, but did not reduce the incidence of symptomatic vasospasm. No patients who had received ventricular drainage or external decompression developed fatal vasospasm.

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Numerous approaches to the prevention and treatment of cerebral vasospasm have been reported recently, but the effect of these methods is still controversial. The authors have evaluated the effect of administering cisternal irrigation with nicardipine-Ringer solution (0.01mg/ml) or continuous intravenous nitroglycerin (GTN) infusion to prevent cerebral vasospasm.
One hundred forty consecutive patients classified as CT Group 3 or 4 were operated on within 48 hours after subarachnoid hemorrhage due to cerebral aneurysm. In nineteen cases, cisternal irrigation with nicardipine was carried out for 14 days on an average after aneurysmal clipping. Another fifteen patients were treated with continuous intravenous infusion of GTN (0.5-1.0μg/kg/min.).
Neither method prevented angiographic vasospasm, but they reduced the severity of the vasocontraction. They significantly reduced the mortality of aneurysm surgery in high-risk patients. In each group, good or excellent results were obtained in almost half of the cases, and no fatality due to vasospasm occurred. These results indicate that both cisternal irrigation with nicardipine and continuous intravenous GTN infusion may prevent severe vasospasm and improve the prognosis of serious subarachnoid hemorrhage due to a ruptured aneurysm.

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We had 919 cases of subarachnoid hemorrhage (SAH) caused by a ruptured intracranial aneurysm from January, 1979 to April 1987. Of these cases, We operated on 546 cases within 72 hours after onset. Of these 546 cases, 137 were classified as Hunt and Kosnik Grade IV & V preoperatively. Since January, 1984, we have performed hemodilution therapy for prevention of post-SAH angiospasm. We term the period before December, 1983, the “No-Hemodilution Period” and the period after January, 1984 the “Hemodilution Period” The landmark of the Hemodilution Therapy was the hematocrit value of day 7 after onset. In the No-Hemodilutin period the mean value of hematocrit fo 253 cases was 36.7% and in the Hemodilution period that of 150 cases was 31.9%. The difference is statistically significant. In the cases of Hunt and Kosnik Grade IV & V the difference of 37.4% and 31.9% is significant.
On the Glasgow Outcome Scale in the No-Hemodilution period the percentage of Good Recovery was 35.6% and of Death was 30.9%, and in the Hemodilution period the corresponding percentages were 56.8% and 18.8%. These differences are statistically significant. In the cases of Hunt and Kosnik Grade IV & V in the No-Hemodilution period the percentage of Good Recovery was 6.8% and of Death was 52.7% and in the Hemodilution period that the corresponding percentages were 31.7% and 34.9%. The differences are significant. We submit that hemodilution therapy is effective for the perevention of symptoms of anaiospasm.

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Medical treatment of patients with severe subarachnoid hemorrhage (SAH) and severe vasospasm still poses many problems and the prognosis of these patients is poor. In the present study, we performed barbiturate therapy on 22 cases of severe SAH and 17 cases of severe vasospasm, and obtained good results. One third of the 22 cases of severe SAH treated with barbiturate had an excellent outcome, another 1/3 a good outcome and the last 1/3 a poor otucome. Barbiturate therapy was especially effective with cases accompanied by intracerebral hematoma. In addition, early initiation of the therapy and/or long-term continuation of the therapy for more than two weeks tended to result in a good outcome.
On the other hand, the effectiveness of barbiturate therapy on the 17 cases of severe vasospasm was not necessarily good (the mortality rate reached 41%). In these spasm cases, barbiturate therapy was more effective when the therapy was started before the level of consiousness decreased to stupor. Also, it should be kept in mind that the decrease of blood pressure at the start of the barbiturate therapy can possibly aggravate the cerebral ischemia; therefore, the control of blood pressure is critical factor in the effectiveness of the therapy.
The following side effects of the therapy were noted in our series: 15 cases of liver malfunction (38%), 10 cases of hypotension (26%), four cases of pneumonia (10%) and two cases of pancreatitis (5%). One of the patients complicated with pneumonia died, suggesting that respiratory control to prevent pneumonia is important during the therapy.

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Barbiturate coma therapy was employed in six patients with subarachnoid hemorrhage of grade III and IV to prevent cerebral infarction due to vasospasm after rupture of a cerebral aneurysm. A thick subarachnoid clot and tight brain were shown on CT scans in all of the patients.
Barbiturate coma therapy was begun between one and nine days (mean, 5.5 days) after subarachnoid hemorrhage and continued for 49 to 98 hours (mean, 69.3 hours). It was maintained with a continuous intravenous infusion of between 5 and 10mg/kg/hour of thiamylal sodium to achieve burst suppression on the electroencephalogram.
Two patients recovered with no neurological deficits, one patient was left in a persistent vegetative state, and three patients died. One of the patients who died recovered to an alert state after barbiturate coma therapy but died from pulmonary embolism 40 days after the subarachnoid hemorrhage.
From a reveiw of these six cases, we consider it appropriate for grade IV patients with increased intracranial pressure to receive barbiturate coma therapy immediately after operation and for grade III patients with increased intracranial pressure to receive it immediately after the onset of delayed neurological deficits due to vasospasm.

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Little information has been available about the fact that the incidence of severe SAH differs among hospitals, though the fact is important as a basis of many statistical analyses of SAH. We, therefore, investigated in this study the difference in severity of SAH among hospitals and considered the cause of the variation. SAH caused by aneurysmal rupture (1064 cases in the total) in each of sixteen hospitals with different emergency systems was analyzed from the standpoint of the Hunt and Kosnik grading at admission and the timing of admission. All the patients admitted to a hospital were investigated in six hospitals (Group A) and only the patients admitted to the neurosurgical department were investigated in ten other hospitals (Group B). The distribution patterns of the Hunt and Kosnik grading (grade-patterns) varied widely among seven hospitals that had more than 50 cases, especially in the rate of Grade V (2.9% to 37%). Next, the Group A cases were investigated from the standpoint of timing of admission. The rate of Grade V was about three times higher in patients of day 0 admission (24.8%) than in those of d 1-d 3 admission (8.5%). Analyzing the timing of admission we found two types of hospital: Type 1 that mainly received emergency cases (d 0 patients>70%), and Type 2 that mainly received cases from affiliated hospitals (d 0 patients<30%). The rate of Grade V in the Type 1 hospitals (26.1%) was about three times higher than that of the Type 2 hospitals (7.0%). This result indicated that a considerable number of Grade V patients were excluded before admission in the Type 2 hospitals. The rate of Grade V on d 0 was about three times higher in Group A (24.8%) than in Group B (8.7%). The results indicated that the inoperable cases admitted to internal medicine were excluded from the list of neurosurgery candidates. However a comparative study of d 0 cases among hospitals of Group A still showed a wide variety in the rate of Grade V patients (14.5%-43.5%). The results seemed to indicate that severe SAH cases were unequally distributed among hospitals in the process of direct delivery from the place of onset. In conclusion it is assumed that patients with severe SAH had three screenings in the course of admission.
1. Screening by the emergency transfer route.
2. Screening before admission to Type 2 hospitals.
3. Screening by the department in the hospital.

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261 cases with ruptured cerebral aneurysms who had undergone early surgery within 72 hours after the last rupture were evaluated from the point of their preoperative neurological severity on the WFNS SAH grading and the Hunt and Kosnik grading, and the relation to the outcome after six months was analyzed.
Although in evaluation by Hunt and Kosnik grading, many cases (42.1% of all) were classed as Grade III, which indicates an unpriedictable outcome, evaluation by WFNS grading placed them in Grade II, which indicates patients who can expect a good prognosis, and Grade IV, which indicates patients with poor prognosis. However, some cases (13.2%) of WFNS Grade V showed good recovery, so that to exclude cases whose WFNS grading does not indicate early surgery may run some risk of losing patients who actually have a good prognosis.

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In order to clarify the relationship between the operative results and W.F.N.S. grading of patients who underwent early surgical intervention, 58 patients with ruptured aneurysms were investigated. The 58 cases were rated Hunt-Kosnik Grade III and IV. There was no significant difference in outcome or operative procedure between Hunt-Kosnik Grade III and IV. On the other hand, these 58 cases measured on the W.F.N.S. grading broke down into Grades II, III, IV, and V. Using W.F.N.S. grading, the outcome and operative procedure were significant differant between Grades II-III and Grades IV-V. But there was not much difference in outcome or operative procedure between W. F. N. S. Grade II and III, and between Grade IV and V. In addition, 30% of the patients rated Grade IV and V obtained a good outcome more often than mild disability. (Glasgow Outcome Scale) From these results it is concluded that W.F.N.S. grading is superior to Hunt-Kosnik grading from the aspect of operative results, but the existance of patients who achieve a outcome in spite of their poor grade is the point at issue.

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We analyzed clinical courses and overall management results in patients with severe subarachnoid hemorrhage of Grade IV or V (Hunt and Kosnik), on the basis of CT findings within 48 hours after the ictus. CT findings were classified into the following four types: Subarachnoid hemorrhage (SAH) only (Type I), with intraventricular hemorrhage (Type II), with intracerebral hematoma (Type III) and with acute subdural hematoma (Type IV).
Our policy of surgical treatment for patients in the acute stage was as follows: Clipping of aneurysm with removal of subarachnoid clots was performed in all cases within 48 hours after onset, except for Grade V cases not having middle cerebral aneurysms and for Grade IV and V cases with posterior circulation aneurysms. Surgery for these cases not included above was postponed until various conservative treatments brought about improvement in neurological conditions.
Thirty-five percent of the patients were Type I, 27%-Type II, 27%-Type III and 11%-Type IV. The mortality rate was 52% in Type I, 75% in Type II, 44% in Type III and 71% in Type IV. Type II and IV initial CT scans suggested a poor prognosis ending in death, while Type III suggested a good prognosis. In patients with Type I or II scans, the poor clinical results were attributable to diffuse acute brain swelling, postoperative vasospasm and systemic complications. Massive intracerebral hematoma or associated subdural hematoma was the major cause of poor outcome in patients with Type III or IV scans. Twenty-seven percent of patients operated on the day of admission (early surgery group) had a favorable outcome. On the other hand, 14% of patients whose surgery was delayed until their neurological conditions had improved (late surgery group) had favorable outcome. The mortality rate in the early surgery group was 43%, while that in the late surgery group was 50%.
It was suggested that our CT classification was clinically helpful in predicting prognosis of patients with severe SAH and for deciding surgical procedures. Moreover, our results suggest that early surgery might be indicated for critically-ill patients with SAH.

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