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Object: The objective of the present study was analysis of results of the prospective clinical trial directed toward the evaluation of therapeutic efficacy of the administration of autologous formalin-fixed tumor vaccine (AFTV) concomitant with fractionated radiotherapy in cases of newly diagnosed glioblastoma multiforme., Methods: Twenty-four patients were enrolled into the clinical trial, while 2 cases were excluded from the final analysis of results. The treatment protocol included aggressive tumor resection, fractionated radiotherapy up to a total dose of 60 Gy, and 3 concomitant courses of AFTV administered with an interval of one week at the late stage of irradiation. Two delayed-type hypersensitivity (DTH) tests were done--one 48 hours before the initial course of vaccination (DTH-1) and one 2 weeks after the third (DTH-2). All but one of the patients received salvage therapy at the time of tumor progression. The defined primary end point was overall survival; secondary end points were progression-free survival and safety of concomitant treatment., Results: The median duration of overall survival was 19.8 [corrected] months (95% CI 13.8-31.3 months). The actuarial 2-year survival rate was 40%. The median duration of progression-free survival was 7.6 months (95% CI 4.3-13.6 months). Overall survival showed a statistically significant association with recursive partitioning analysis class (p < 0.05); progression-free survival showed a statistically significant association with p53 staining index (p < 0.05) and size of DTH-2 response (p < 0.001). AFTV injection concomitant with fractionated radiotherapy was well tolerated by all patients and in no case did treatment-related adverse effects exceed Grade 1 toxicity; adverse effects were limited to local erythema, induration, and swelling at the site of injection., Conclusions: The results of this study demonstrate that AFTV treatment concomitant with fractionated radiotherapy may be effective in patients with newly diagnosed glioblastoma. Further clinical testing is warranted.

Abducent nerve schwannomas are extremely rare. The authors recently performed Gamma Knife surgery (GKS) in 4 patients with such tumors and describe their experiences with these cases. The patients consisted of 3 women and 1 man whose ages varied from 31 to 60 years (mean 46 years). Two patients had no symptoms, 1 complained of slight visual disturbances, and the other 1 had abducent nerve palsy. Neurofibromatosis was not diagnosed in any case. All 4 tumors were located in the cavernous sinus: 2 of these tumors within the borders of the sinus, 1 tumor extending into the orbit, and 1 tumor extending into the prepontine cistern. The volume of the neoplasms varied from 1.7 to 4.9 cm(3) (mean 3.0 cm(3)). No patient underwent tumor resection. Treatment was delivered with the aid of a Leksell Gamma Knife model C unit and the automatic positioning system. The dose directed to the tumor margin was 12 Gy in all cases. The dose directed to the anterior visual pathways was kept below 10 Gy and that to the brainstem below 14 Gy. The length of follow-up varied between 7 and 43 months (mean 27 months). There were no acute complications or side effects. Imaging studies showed temporary enlargement of all tumors during the 1st posttreatment year, but thereafter, there was a trend toward reduction in volume. None of the neoplasms displayed regrowth. In the 3 patients who did not have abducent nerve palsy before GKS, it appeared, at least temporarily, after the procedure. Purely intracavernous neoplasms in general followed uneventful posttreatment courses, but dumbbell-shaped tumors were associated with significant morbidity. The cisternocavernous schwannoma underwent cystic degeneration 2 years after GKS, and the patient developed diplopia. After GKS, the patient treated for an orbitocavernous schwannoma experienced a significant deterioration in vision, temporary blindness in 1 eye, and late development of permanent abducent nerve palsy, which were seemingly caused by compression of neurovascular structures within the anulus of Zinn during a temporary increase in the lesion's volume after irradiation. Gamma Knife surgery controls the growth of abducent nerve schwannomas and may be effectively used to manage intracavernous neoplasms. Caution, however, should be used in cases of dumbbell-shaped tumors, particularly those extending through the superior orbital fissure.

Object: Stereotactic radiosurgery for brain metastasis has become one of the standard treatment options in recent years. Some patients must undergo repeated stereotactic radiosurgery for new lesions. The authors retrospectively reviewed their data to estimate how soon the patients undergo repeated radiosurgery for new lesions., Methods: Between October 1999 and March 2006, 1081 patients with brain metastases underwent Gamma Knife surgery (GKS) at Tokyo Women's Medical University. One hundred and forty-nine patients in whom GKS had been performed two or more times were evaluated. There were 68 men and 81 women with a median age of 61 years (range 29-90 years). The authors analyzed data on patient age, number of treated lesions, and period between GKSs. Follow-up imaging was performed in almost all patients every 2 to 3 months after GKS. The number of lesions treated in a single session varied from one to 35. The median interval between GKSs was 26 weeks (range 3-175 weeks) for patients with breast cancer and 23 weeks (range 4-179 weeks) for patients with non-small cell lung carcinoma., Conclusions: It would appear that follow-up imaging studies should be obtained every 2 to 3 months after GKS to monitor patients for tumor recurrence.

Gamma Knife surgery (GKS) is image-guided surgery for brain tumors. Precise tumor visualization is needed in dose planning to control tumor progression. The surrounding vital structures must also be clearly defined to allow the preservation of their function. A special magnetic resonance (MR) imaging sequence was chosen for use with GKS to treat skull base and suprasellar tumors. Gadolinium-enhanced 0.5-mm constructive interference in steady-state (CISS) slices were obtained in skull base and suprasellar tumors. Each structure that was adjacent to the tumor could be visualized more clearly by using this imaging technique because the tumor became transparent even though there was no change in the appearance of the surrounding structures after injection of Gd. Use of this technique in acoustic tumors allowed the seventh and eighth cranial nerves to be visualized in the cisternal and intrameatal portions; both of which were distinguishable from the tumor. Suprasellar tumor could be distinguished from the adjacent optic pathway. The use of Gd-enhanced CISS imaging allowed for optimal dose planning with very high conformity in every tumor. Achieving this high conformity allowed the preservation of adjacent structures and their functions. Establishing optimal dose planning in brain tumors is very important to overcome the problem of producing new neurological deficits in patients who may already be suffering disease-related deficits. The use of this special CISS MR imaging sequence may help accomplish this goal.

Object: Gamma Knife surgery (GKS) is becoming a standard treatment for vestibular schwannoma (VS); it is ranked with microsurgery from the perspective of tumor control and audiofacial nerve function preservation. A new treatment technique that will improve the tumor shrinkage ratio, shorten the patient's recovery time, and even recover some cranial nerve function is described., Methods: Along with advances in the GKS system, the authors have developed magnetic resonance imaging sequences specific to particular treatments. These newly developed sequences provide much clearer visualization of the distribution of the cranial nerves, especially in the area from the cisterns to the internal acoustic meatus. Magnetic resonance images have been fused with computed tomography scans to facilitate better delineation of the anatomical relationships. These dose-planning images allow for a higher isodose line (80%) inside the tumor. The aim is to shrink the tumor and not just to control it. To date 130 patients have been treated with GKS in conjunction with this new technique. Of the 130, 91 patients were observed for more than 12 months. The tumor shrinkage rate was 65.9% (76% for patients with > 24 months of follow up), the facial nerve preservation rate was 98.9%, the hearing preservation rate was 92.3%, and four (4%) of 91 patients recovered hearing function. Transient tumor enlargement was observed in most cases, but no severe complications were found., Conclusions: Although these results are preliminary, they would appear to represent a potential breakthrough in the treatment of VS. Longer follow-up periods and additional cases will firmly establish this method as an absolute treatment option for patients with a VS.

Object: The authors analyzed of the long-term complications that occur 2 or more years after gamma knife surgery (GKS) for intracranial arteriovenous malformations (AVMs)., Methods: Patients with previously untreated intracranial AVMs that were managed by GKS and followed for at least 2 years after treatment were selected for analysis (237 cases). Complete AVM obliteration was attained in 130 cases (54.9%), and incomplete obliteration in 107 cases (45.1%). Long-term complications were observed in 22 patients (9.3%). These complications included hemorrhage (eight cases), delayed cyst formation (eight cases), increase of seizure frequency (four cases), and middle cerebral artery stenosis and increased white matter signal intensity on T2-weighted magnetic resonance imaging (one case of each). The long-term complications were associated with larger nidus volume (p < 0.001) and a lobar location of the AVM (p < 0.01). Delayed hemorrhage was associated only with incomplete obliteration of the nidus (p < 0.05). Partial obliteration conveyed no benefit. Delayed cyst formation was associated with a higher maximal GKS dose (p < 0.001), larger nidus volume (p < 0.001), complete nidus obliteration (p < 0.01), and a lobar location of the AVM (p < 0.05)., Conclusions: Incomplete obliteration of the nidus is the most important factor associated with delayed hemorrhagic complications. Partial obliteration does not seem to reduce the risk of hemorrhage. Complete obliteration can be complicated by delayed cyst formation, especially if high maximal treatment doses have been administered.

Object: Although reports in the literature indicate that thalamic pain syndrome can be controlled with chemical hypophysectomy, this procedure is associated with transient diabetes insipidus. It was considered reasonable to attempt gamma knife surgery (GKS) to the pituitary gland to control thalamic pain., Methods: Inclusion criteria in this study were poststroke thalamic pain, failure of all other treatments, intolerance to general anesthetic, and the main complaint of pain and not numbness. Seventeen patients met these criteria and were treated with GKS to the pituitary. The target was the pituitary gland together with the border between the pituitary stalk and the gland. The maximum dose was 140 to 180 Gy. All patients were followed for more than 3 months., Conclusions: An initial significant pain reduction was observed in 13 (76.5%) of 17 patients. Some patients experienced pain reduction within 48 hours of treatment. Persistent pain relief for more than 1 year was observed in five (38.5%) of 13 patients. Rapid recurrence of pain in fewer than 3 months was observed in four (30.8%) of 13 patients. The only complication was transient diabetes insipidus in one patient. It would seem that GKS of the pituitary might have a role to play in thalamic pain arising after a stroke.

The authors conducted a study to determine a way of overcoming the poor-quality demonstration of choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) on conventional magnetic resonance (MR) imaging studies. The poor MR imaging demonstration of CNV in patients with AMD makes the use of gamma knife surgery more difficult. This difficulty, however, can be overcome by use of a modified time-of-flight MR imaging,sequence with Gd enhancement and coronal reconstruction.

Object: A large number of clinical studies have been made on treatment outcomes of radiosurgery for arteriovenous malformations (AVMs), but the reported obliteration rates following this treatment vary significantly, perhaps reflecting the different methods and timings of the imaging studies used., Methods: The authors retrospectively analyzed their experience with gamma knife surgery in 400 patients with AVMs (follow-up period 1-135 months, median 65 months), with special reference to the imaging modality used in each case. The calculated obliteration rates varied from 68.2 to 92%, depending on imaging modality and timing of evaluation. When only unquestionable imaging data such as demonstrations of a residual nidus on computerized tomography (CT) or magnetic resonance (MR) images or findings on angiograms were used in the calculation, the obliteration rates were 72% at 3 years and 87.3% at 5 years. Factors leading to a better obliteration rate were previous hemorrhage (p = 0.0084), smaller nidus (p = 0.0023), and higher radiation dose to the lesion's margin (p = 0.0495), as determined in a multivariate analysis. Factors leading to an earlier obliteration of the nidus were male sex (p = 0.0001), previous hemorrhage (p = 0.0039), smaller nidus diameter (p = 0.0006), and dose planning using angiography alone (p = 0.0201)., Conclusions: After the introduction of CT and MR images into dose planning, the conformity and selectivity of dosimetry improved remarkably, although the latency intervals until obliteration were prolonged. Imaging outcomes for AVMs should be evaluated using data provided by longer follow-up periods. The timing of additional treatments for residual AVMs should be decided cautiously, considering the size of the AVM, the patient age and sex, and the history of hemorrhage before radiosurgery.

Object: The purpose of this study was the analysis of a large series of patients treated with gamma knife radiosurgery for pituitary adenoma in a single institution., Methods: One hundred eight patients with pituitary adenomas were treated over the last 7 years. Seventy-four patients have been followed for more than 6 months and form the basis of this report., Conclusions: Twenty-three patients harbored nonfunctioning adenomas, and 56 harbored functioning adenomas. The mean margin dose was 22.5 Gy (nonfunctioning adenomas, 19.5 Gy; functioning adenomas, 23.8 Gy). Control of tumor growth was achieved in 91%. A significant decrease of excessive hormone production was seen in 80% of patients, and the endocrinological normalization rate was 30.3%. Postradiosurgical complications were seen in 2.5%.

The authors conducted a multiinstitutional phase II study to establish a postsurgical combined chemotherapy and radiation therapy regimen for patients with primary germ cell tumors of the brain. After surgical debulking of the tumor and histological verification, patients were divided into three therapeutic groups: good prognosis, intermediate prognosis, and poor prognosis. Patients received two kinds of chemotherapy (three courses) prior to receiving radiation therapy: carboplatin-etoposide combination ([CARB-VP]: carboplatin 450 mg/m(2) on Day 1, etoposide 150 mg/m(2) on Days 1-3) or ifosphamide-cisplatin-etoposide combination ([ICE]: ifosphamide 900 mg/m(2), cisplatin 20 mg/m(2), and etoposide 60 mg/m(2) on Days 1-5). Patients in the good prognosis group (those with germinomas) were treated with CARB-VP followed by local radiation therapy (24 Gy). Patients in the intermediate prognosis group received CARB-VP followed by local radiation therapy (50 Gy); they received five additional chemotherapy treatments. Patients in the poor prognosis group received ICE followed by whole craniospinal radiation therapy; they also received five additional chemotherapy treatments. Eighty-two patients were evaluated. For the 56 patients with germinomas, a 93% rate of complete remission after treatment was achieved. The remission rate was 76% for 21 patients in the intermediate prognosis group, and no recurrence was detected during a median follow-up period of 2.6 years. In the group of five patients with poor prognosis, the disease in three patients progressed during chemotherapy or radiation therapy and they died within 6 months. There were no serious complications in the surviving patients. The authors found their treatment protocols to be currently effective for patients with germinomas and those with an intermediate prognosis.

Object: Because arteriovenous malformations (AVMs) in the basal ganglia and thalamus are difficult to treat, the authors conducted a retrospective study to determine the best management strategy for these lesions., Methods: The authors reviewed the management and outcome in 101 patients with AVMs treated between 1971 and 1995. In 15 conservatively treated patients, hemorrhage occurred in 71.4% (annual rate 11.4%), and the morbidity and mortality rates were 7.1% and 42.9%, respectively, during a mean follow-up period of 6.6 years. Total microsurgical resection was performed in 15 patients with no mortality resulting, but motor function deteriorated permanently in three of them (20%). Postoperative morbidity correlated well with the location of the AVM and with preoperative motor function. In cases of lenticular AVMs without motor weakness, a postoperative decrease in motor function was significantly more common than in the remaining patients. In patients with motor weakness before surgery, AVMs in the thalamus or caudate nucleus were successfully resected. Among 66 patients treated with gamma knife radiosurgery, three had permanent radiation-induced neurological deficits, and three others experienced bleeding (new bleeding in one case and rebleeding in two). The treatment-associated morbidity rate was 6.7%, and the actuarial rate of complete obliteration was 85.7% at 2.5 years. In five patients treated with embolization alone, the morbidity and mortality rates associated with the procedure or bleeding were 40% and 20%, respectively. The morbidity and mortality rates in the pre-gamma knife era were 22.2% and 22.2%, whereas those for the post-gamma knife era are currently 10.4% and 1.5%, respectively., Conclusions: These results indicate that conservatively treated AVMs are more likely to bleed and thus produce a high incidence of patient mortality. Multimodal treatment including radiosurgery, microsurgery, and embolization improved clinical outcomes by making it possible to treat difficult cases successfully.

The authors analyzed 153 cases of histologically verified intracranial germ cell tumors. The histological diagnosis was germinoma in 63 patients (41.2%), teratoma in 30 (19.6%), and other types of tumors in 60 patients (39.2%). The patients were treated by a consistent policy of surgical removal with histological verification followed by radiation therapy with or without chemotherapy. The 10- and 20-year survival rates of patients with pure germinoma were 92.7% and 80.6%, respectively. The 10-year survival rates of patients with mature teratoma and malignant teratoma were 92.9% and 70.7%, respectively. Patients with pure malignant germ cell tumors (embryonal carcinoma, yolk sac tumor, or choriocarcinoma) had a 3-year survival rate of 27.3%. The mixed tumors were divided into three subgroups: 1) mixed germinoma and teratoma; 2) mixed tumors whose predominant characteristics were germinoma or teratoma combined with some elements of pure malignant tumors; and 3) mixed tumors with predominantly pure malignant elements. The 3-year survival rates were 94.1% for the first group, 70% for the second group, and 9.3% for the third group, and the differences were statistically significant. Twenty-six patients with malignant tumors received chemotherapy that consisted of cisplatin and carboplatin combinations with or without radiation therapy. However, chemotherapy was not significantly more effective than radiation therapy alone. From these treatment results, the authors classified tumors into three groups with different prognoses and proposed a treatment guideline appropriate for the subgroups.

A water-soluble, novel synthetic compound, AVS ((+/-)-N, N'-propylenedinicotinamide; nicaraven) has no demonstrable vasoactive properties but scavenges hydroxyl radicals in aqueous environmental conditions at neutral pH. Based on the results of preceding experimental and clinical studies showing marked ameliorative effects of AVS on cerebral vasospasm and ischemic brain damage, a multicenter, placebo-controlled double-blind clinical trial was undertaken to verify its beneficial effects on delayed ischemic neurological deficits (DINDs) due to vasospasm and on the overall outcome of patients with subarachnoid hemorrhage (SAH). A total of 162 patients with SAH who had Glasgow Coma Scale scores between 7 and 15 on admission were enrolled in the trial. Drug administration (4 g AVS or 4 g glucose as placebo; infused intravenously for 6-8 hours once a day) was begun within 5 days post-SAH and continued for 10 to 14 days. Intent-to-treat analysis of these patients revealed that the overall incidence of DINDs, which was defined as an exacerbation of impaired consciousness and/or focal neurological deficits, was significantly reduced, by 34.5% (placebo 54.2%, AVS 35.5%; p < 0.05, Mann-Whitney U-test). The Glasgow Outcome Scale (GOS) score at 1 month was significantly improved by AVS (p < 0.05, U-test). At 3 months, the difference in the GOS scores between the groups became marginal on U-tests (p < 0.10), but the percentage of good outcome tended to increase, with a relative increase of 20.3% (AVS 76.3%, placebo 63.4%; p < 0.10, chi-square test), and the cumulative incidence of death was significantly reduced (p < 0.05, log-rank test). No significant adverse reaction attributable to treatment was observed. the usefulness of AVS in therapy for SAH is strongly indicated by the fact that the agent significantly ameliorated DINDs, leading to a marked improvement in the GOS scores at 1 month, as well as a reduction in the cumulative incidence of death by 3 months.

The present study was undertaken to determine whether oxyhemoglobin (OxyHb) is responsible for the functional alterations in the cerebral arteries observed during chronic vasospasm after subarachnoid hemorrhage. Vascular strips of canine basilar arteries were kept in organ culture for 3 days with or without repetitive exposure to OxyHb (OxyHb-treated and control strips). Contractions elicited by high levels of potassium (80 mM) and uridine 5'-triphosphate (3 x 10(-4) M) were reduced in the OxyHb-treated group in a concentration-dependent manner. The relaxations evoked by nitric oxide and 8-bromo-cyclic guanosine monophosphate (8-bromo-cGMP) were not affected. Relaxations elicited by the calcium channel blocker, diltiazem, were attenuated in the OxyHb-treated rings. When the extracellular calcium concentration ([Ca2+]e) was changed from a concentration in the external solution of 10(-8) M to 10(-3) M, myogenic tension developed. Myogenic tension, expressed as a percentage of the maximum contraction in each segment, was augmented in the OxyHb-treated group at [Ca2+]e of 10(-5) M and 10(-4) M. There were no significant differences in passive compliance of the arterial wall between the two groups. These results demonstrated that prolonged exposure to OxyHb in vitro results in a decrease in contractile capacity and an increase in sensitivity to [Ca2+]e, in agreement with previous findings in spastic arteries. By contrast, impairment of the 8-bromo-cGMP-mediated relaxation pathway and increased stiffness of the arterial wall, which have been reported to occur in spastic arteries, were not induced by prolonged exposure to OxyHb in vitro.

The question of whether unruptured intracranial vertebral artery dissections should be treated surgically or nonsurgically still remains unresolved. In this study, six consecutive patients with intracranial vertebral artery dissection presenting with brain-stem ischemia without subarachnoid hemorrhage (SAH) were treated non-surgically with control of blood pressure and bed rest, and five received follow-up review with serial angiography. No further progression of dissection or associated SAH occurred in any of the cases, and all patients returned to their previous lifestyles. In the serial angiograms in five patients, the findings continued to change during the first few months after onset. Four cases ultimately showed "angiographic cure," while fusiform aneurysmal dilatation of the affected vessel persisted in one case. In one patient, arterial dissection was visualized on the second angiogram despite negative initial angiographic findings. These results indicate that intracranial vertebral artery dissection presenting without SAH can be treated nonsurgically, with careful angiographic follow-up monitoring. Persistent aneurysmal dilatation as a sequela of arterial dissection seemed to form a subgroup of fusiform aneurysms of the posterior circulation. These aneurysms may be prone to late bleeding and may require surgical treatment.

To investigate the pathogenetic significance of metabolic failure observed in spastic cerebral arteries after subarachnoid hemorrhage (SAH), the temporal profile of alterations in the arterial content of high-energy phosphates was studied. A canine model of double hemorrhage was used. Constriction of the basilar artery was measured angiographically on Days 3, 5, 7, and 14 after SAH in separate groups of animals. Adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), guanosine triphosphate (GTP), guanosine diphosphate, creatine phosphate (CrP), and creatine (Cr) levels in the arteries were assayed using high-performance liquid chromatography. A time-dependent development of angiographic spasm was confirmed. A mild vasospasm was seen in the group studied 3 days after SAH, progressed in the Day 5 group, remained comparably severe in the Day 7 group, and resolved partially in the Day 14 group. The content of high-energy phosphates (ATP, GTP, and CrP) declined rapidly over the course of the study, and a significant reduction in ATP, GTP, and CrP was observed in the Day 3 group. Levels of ATP and CrP decreased further in the Day 5 and 7 groups. The decrement in GTP was completed in the early phase; a significant reduction took place in the Day 3 group, with no progression thereafter and no recovery through Day 14. Total adenylate (ATP + ADP + AMP) and total creatine (Cr + CrP) content diminished markedly over the course of the study. These results indicate that metabolic failure and trophic disturbance in the cerebral artery occurs with a rapid onset following SAH and progresses in close association with the development of vasospasm, suggesting a significant causal relationship with the pathogenesis.

The authors present the case of a patient with vertebral artery dissection that rebled after being treated by proximal clipping. This is the second report of such a case. The results indicated that proximal clipping is not free from the risk of rebleeding, and a better alternative surgical technique should always be sought when treating vertebral artery dissections.

With the cooperation of 60 neurosurgical centers in Japan, a prospective randomized placebo-controlled double-blind trial of a new calcium antagonist AT877 (hexahydro-1-(5-isoquinolinesulfonyl)-1H-1,4-diazepine hydrochloride, or fasudil hydrochloride) was undertaken to determine the drug's effect on delayed cerebral vasospasm in patients with a ruptured cerebral aneurysm. A total of 276 patients, who underwent surgery within 3 days after subarachnoid hemorrhage (SAH) of Hunt and Hess Grades I to IV, were entered into the study. Nine patients were excluded because of protocol violation. The remaining 267 patients received either 30 mg AT877 or a placebo (saline) by intravenous injection over 30 minutes, three times a day for 14 days following surgery. Demographic and clinical data were well matched between the two groups. It was found that AT877 reduced angiographically demonstrable vasospasm by 38% (from 61% in the placebo group to 38% in the AT877 group, p = 0.0023), low-density regions on computerized tomography associated with vasospasm by 58% (from 38% to 16%, p = 0.0013), and symptomatic vasospasm by 30% (from 50% to 35%, p = 0.0247). Furthermore, AT877 reduced the number of patients with a poor clinical outcome associated with vasospasm (moderate disability or worse on the Glasgow Outcome Scale at 1 month after SAH) by 54% (from 26% to 12%, p = 0.0152). There were no serious adverse events reported in the AT877 group. This is the first report of a placebo-controlled double-blind trial that has demonstrated a significant reduction in angiographically revealed vasospasm by intravenous drug therapy.

Six patients with severe intraventricular hemorrhage were treated with direct intraventricular infusion of urokinase. In each case, hemorrhage extended into all ventricular chambers, and a cast formation and expansion of the third and fourth ventricles were found. Immediately after the therapy was started (within 7 days from onset of symptoms), reduction of intraventricular hematoma volume was observed on computerized tomography. On average, both the third and fourth ventricles became clear on the third day after hemorrhage; there was one exception, a case of ruptured aneurysm. Five of the six patients showed excellent or good outcome, although two developed delayed hydrocephalus. No infection or rebleeding was observed. The outcome in a retrospectively studied group of five patients not treated with urokinase is also reported. The authors conclude that this relatively easy method of treatment will greatly improve the prognosis of severe intraventricular hemorrhage.

The purpose of this experiment was to study the nature of vasoactive substance in cerebrospinal fluid (CSF) from patients with aneurysmal subarachnoid hemorrhage. The authors have examined the effects of disulfide bond-reducing agents, a sulfhydryl group oxidizing agent, and specific antagonists of so-called "classical" neurotransmitters on the in vitro isometric contraction of canine basilar arterial strips induced by bloody human CSF. The disulfide bond-reducing agents dithiothreitol (10(-4) M) and dithioerythritol (10(-4) M) suppressed the contraction induced by bloody CSF by an average of 40.3% and 61.2%, respectively. This suppression was achieved under conditions that did not alter KCl-induced contraction. The sulfhydryl group oxidizing agent, 5,5'-dithiobis-(2-nitrobenzoic acid), 10(-4) M, reversed the inhibitory effect of dithioerythritol on the contractile response to bloody CSF. No significant suppression of any response in any preparation was observed with methysergide (10(-7) M), mepyramine (10(-7) M), phenoxybenzamine (10(-5) M), propranolol (10(-6) M), or atropine (10(-6) M). These results indicate that disulfide bonds in the arterial smooth-muscle cells are involved in the contractile responses of canine basilar artery to bloody CSF. Prostaglandins, hemoglobin, and lipid hydroperoxides may all be spasmogens in bloody CSF, while serotonin, histamine, norepinephrine, and acetylcholine are probably not involved.

The authors have developed a fluoroscopy-assisted technique of percutaneous radiofrequency facial nerve coagulation at or near the stylomastoid foramen for management of facial spasm. The details of the procedure and the operative results in the initial series of 27 cases of facial spasm are described. The series included six men and 21 women, aged from 16 to 73 years. Twenty-four patients had classical, intractable, persistent hemifacial spasm, one had an unusual bilateral facial spasm, and one a postparalytic facial spasm. The age of onset varied from 16 years to 70 years. The duration of the symptoms ranged from 3 months to 11 years. Ten patients had undergone previous blunt-needle compression of the facial nerve from one to 10 times. The operative results in the 27 patients have so far been excellent. The longest follow-up has been 1 1/2 years. Although partial facial weakness was present in 60% of the cases, it invariably disappeared within 1 to 4 months. Only three patients experienced recurrence of spasm. In two of them, recurrence followed low-temperature coagulation. The procedure is simple, easy to perform, and extremely effective. It can be performed under local anesthesia in the outpatient clinic.

A series of 125 patients who underwent surgery for craniopharyngiomas was evaluated to assess the efficacy of radiation therapy: 45 patients had received radiotherapy and 80 had not. These patients included all operative survivors (excluding cases with total tumor removal) treated during the 30 years from 1950 to 1979. Median survival time of the irradiated group was greater than 10 years, whereas it was 3.12 years for the nonirradiated (or control) group. The 5- and 10-year survival rates were 88.9% and 76.0% for the irradiated group, and 34.9% and 27.1% for the control group, respectively. Overall comparison, using the Lee-Desu statistical method, revealed that there was a very high statistical significance (at the level of p less than 0.0001) in the difference between the survival times of the irradiated and control groups. The influence of the following factors on the effectiveness of radiotherapy was analyzed: age of the patient at the first operation, sex, date of surgery, the extent of tumor removal, the size of the tumor, the composition of the tumor (cystic or solid), whether the tumor was calcified or not, the histological subtype of the tumor, the presence of intracranial hypertension, the grade of visual failure, and the presence or absence of diabetes insipidus, altered mentation, and adiposogenital syndrome. The results indicated that, when total removal of the tumor is impossible, radiotherapy should be administered.

The efficacy of thromboxane synthetase inhibitor in the prevention of cerebral vasospasm after subarachnoid hemorrhage (SAH) was evaluated in a prolonged experiment using dogs. Changes in the diameter of the basilar artery were followed by angiography, and morphological changes were studied by photomicroscopy and electron microscopy. As a thromboxane synthetase inhibitor, OKY-1581 (sodium-(E)-3-(4(-3-pyridylmethyl)phenyl)-2-methylacrylate) was used. Dogs received intravenous injections of 160 mg of OKY-1581 dissolved in 2 ml of physiological saline immediately after subarachnoid blood injection. Subsequently, the animals received continuous intravenous infusion of the drug at the rate of 4 gm/50 ml/24 hours until sacrifice 4 days after induction of SAH. Control dogs received subarachnoid blood injection without treatment with OKY-1581. Angiographic examination revealed that the late spasm was almost completely abolished by the treatment with OKY-1581. Early spasm was also prevented, but the drug's effect was less prominent than it was on the late spasm. Morphological study revealed degenerative changes in the endothelium and myonecrotic changes in the tunica media following SAH in the basilar arteries of the treated as well as the untreated dogs. However, corrugation of the internal elastic lamina was almost completely absent in the treated dogs. The above results indicate that a disproportionate synthesis of thromboxane A2 plays an important role in the evolution of chronic cerebral vasospasm following SAH, and that drugs such as OKY-1581 that selectively inhibit thromboxane synthetase might be useful in the prevention of vasospasm.

A rare case of leiomyosarcoma arising from the dura mater is presented. A definite histological diagnosis was based on the electron microscopic features. Extensive removal of the tumor and postoperative radiation therapy resulted in complete remission. The etiology and the origin of this tumor are discussed.

An extremely rare case of isolated histioproliferative lesions arising from the subarachnoid space of the left occipital convexity and the orbit is presented. The presence of histiocytes showing lymphophagocytosis and positivity for S-100 protein staining confirmed that the lesions represented extranodal forms of sinus histiocytosis with massive lymphadenopathy.

The authors describe two cases of malignant astrocytomas associated with previous radiation therapy in childhood for intracranial germinoma and craniopharyngioma. In both patients, there was no recurrence at the primary tumor site. Because of a geometric coincidence between the tumor location and the radiation field, radiotherapy was strongly implicated as a cause of these two astrocytomas.

A randomized clinical study of irradiation and irradiation combined with ACNU in the treatment of malignant gliomas was performed in order to determine if there was an enhancing therapeutic effect of ACNU given in addition to radiotherapy. An effect was defined as a reduction in tumor size, changes in neurological signs and performance status within 1 month after the completion of radiotherapy, or statistically improved survival times. Seventy-seven patients from 14 neurosurgical clinics were included in this validated study group. Radiotherapy with a total dose of 5000 to 6000 rads, given in 25 to 30 subdoses, was applied to the whole brain and to a generous field surrounding the tumor. Patients who were assigned to receive chemotherapy were given ACNU intravenously once or twice during radiotherapy at a dose of 100 mg/sq m of body surface area. The response rate (more than 50% reduction of the tumor size) was 13.5% in the group treated by radiotherapy alone and 47.5% in the group with radiotherapy and ACNU. The hematological toxicity was more severe in the group treated with radiotherapy and ACNU. Other toxicity was mild and acceptable. The survival rates of patients with astrocytoma grade III and glioblastoma multiforme at 36 months after the surgery were 48.9% and 0% for radiotherapy alone and 59.0% and 16.3% for radiotherapy plus ACNU, respectively. The differences between the survival curves were not significant at the p = 0.05 level. This study has demonstrated that, although the use of ACNU during radiotherapy suppressed malignant gliomas more than radiotherapy alone, the survival time was not extended significantly. It is necessary to continue to search for an effective chemotherapeutic regimen to prolong survival of patients with malignant gliomas.