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Tomoki Todo, Masaaki Usui, and Kintomo Takakura

✓ 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.

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Chifumi Kitanaka, Tadashi Morimoto, Tomio Sasaki, and Kintomo Takakura

✓ 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.

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Tomio Sasaki, Susumu Wakai, Takao Asano, Kintomo Takakura, and Keiji Sano

✓ 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.

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Tomokatsu Hori, Takanori Fukushima, Hideo Terao, Kintomo Takakura, and Keiji Sano

✓ 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 1½ 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 lowtemperature coagulation. The procedure is simple, easy to perform, and extremely effective. It can be performed under local anesthesia in the outpatient clinic.

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Kotaro Nakaya, Motohiro Hayashi, Masahiro Izawa, Taku Ochiai, Tomokatsu Hori, and Kintomo Takakura


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.


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.


It would appear that follow-up imaging studies should be obtained every 2 to 3 months after GKS to monitor patients for tumor recurrence.

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Masao Matsutani, Keiji Sano, Kintomo Takakura, Takamitsu Fujimaki, Osamu Nakamura, Nobuaki Funata, and Terukazu Seto

✓ 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.

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Tomio Sasaki, Takao Asano, Kintomo Takakura, Keiji Sano, and Neal F. Kassell

✓ 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.

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Yuhei Yoshimoto, Phyo Kim, Tomio Sasaki, and Kintomo Takakura

✓ 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 though 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.

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Shinya Manaka, Akira Teramoto, and Kintomo Takakura

✓ 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 < 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.