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Masashi Fukui, Akira Tanaka, Katsutoshi Kitamura, and Toshio Okudera

✓ The authors present a surgical case of a lipoma of the cerebellopontine angle in a 28-year-old woman.

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Shunji Nishio, Takatoshi Tashima, Iwao Takeshita, and Masashi Fukui

✓ The clinical and pathological features of six patients with so-called “intraventricular oligodendroglioma” are reported. The tumor had no predilection for sex, and the patients' age at diagnosis ranged from 15 to 39 years. The lesions were located in the lateral and/or third ventricles. Total removal of the tumor was performed in three patients, and the remaining three underwent partial resection. Postoperative irradiation was given to five patients. A follow-up study revealed that five patients were free of recurrent tumor at 15 to 227 months after treatment, and one was alive with disease 25 months after surgery. Histologically, all tumors were composed of small uniform cells, with perinuclear halos and regular round nuclei. Tumor cells were sometimes arranged around nucleus-free fibrillary zones. Mitoses were infrequent. Ultrastructurally, neoplastic cells had round nuclei with dispersed heterochromatin and organelle-sparse cytoplasm containing occasional microtubules, 20 to 25 nm in diameter, and scattered dense-core vesicles, 100 to 200 nm in diameter. Cell processes containing dense-core and clear vesicles were frequently present. Thus, these neoplasms should be considered neuronal in origin, and should be classified as “intraventricular neurocytomas.”

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Tomojirou Nomura, Kiyonobu Ikezaki, Yoshihiro Natori, and Masashi Fukui

✓ The authors studied the effect of intracarotid administration of histamine on the regional cerebral blood flow (rCBF) in transplanted rat C6 glioma by the hydrogen clearance method. Histamine infusion at doses of 1 and 10 µg/kg/min produced an increase of rCBF in the tumor (24.6% ± 16.4%, p < 0.002, and 37.6% ± 18.2%, p < 0.0001, respectively) and also in brain surrounding the tumor (26.8% ± 16.2%, p < 0.002, and 34.9% ± 9.2%, p < 0.0001, respectively) without any significant changes in the ipsilateral hemisphere. Intravenous administration of pyrilamine (H1 antagonist) and cimetidine (H2 antagonist) reduced blood flow responses to histamine; cimetidine was a more effective blocking agent than pyrilamine. Intracarotid infusion of histamine (1 and 10 µg/kg/min) with intravenous injection of Evans blue dye disclosed the selective extravasation of dye in the tumor and the brain surrounding the tumor.

These results indicated that brain tumor vessels could respond to histamine differently than normal brain capillaries. The mechanism of selective response to histamine could be explained either by increased permeability or by altered characteristics of histamine receptors in the tumor vessels.

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Shuji Sakata, Fumio Shima, Motohiro Kato, and Masashi Fukui

✓ To investigate the mechanism of analgesia noted with electrical stimulation of the thalamic sensory relay nucleus and medial thalamus, modulations of neuronal activities in the periaqueductal gray matter (PAG) were studied in response to electrical stimulations of the ventroposterolateral nucleus (VPL) and parafascicular nucleus (Pf) and to peripheral noxious stimulations in rats. Extracellular single-unit activities were recorded from 102 neurons in the PAG and the adjacent area in animals under halothane anesthesia.

A large population (83%) of the PAG neurons reacted to Pf stimulations with a predominantly excitatory response, whereas smaller numbers (43%) responded to VPL stimulations. There was a significant correlation between the response characteristics of Pf and noxious stimulations, whereas no correlation was found between VPL and noxious stimulations. The PAG neurons that were verified antidromically to project to the nucleus raphe magnus showed a similar pattern of response. The excitatory response to the Pf stimulation was partially attenuated by systemic administration of naloxone, whereas that to the VPL stimulation was not affected.

These results suggest that part of the analgesic mechanism of medial thalamus stimulation involves activation of the descending pain suppression system by exciting the PAG neurons through the opioid system, while the analgesia produced by sensory relay nucleus stimulation does not involve the PAG neurons or the opioid system.

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Tooru Inoue, Masashi Fukui, Shunji Nishio, Katsutoshi Kitamura, and Hitoshi Nagara

✓ To test the results of blood-brain barrier (BBB) disruption in the treatment of brain tumor, RG-C6 glioma was transplanted into the brains of rats. Intracarotid infusions of normal saline and hyperosmotic mannitol were then made, followed by intravenous injection of Evans blue dye plus albumin (EB, MW 68,000), horseradish peroxidase (HRP, MW 40,000), and 5-fluorouracil (5-FU, MW 130). Uptake of the drug and the consistency of drug levels in the normal brain and tumor varied widely among these three agents. Both EB and HRP penetrated the brain tumors but did not stain the normal brain tissues. After BBB opening, penetration of EB and HRP into the normal brain was drastically increased; however, the uptake of EB and HRP in the tumor was not increased. The concentration of 5-FU in the tumor was higher than that in the serum and, although it increased 1.5-fold after BBB opening, the increase was not statistically significant. Conversely, there was a progressive increase in concentrations of 5-FU in the tumor-free brain regions (p < 0.05). These observations suggest that an intracarotid infusion of hyperosmotic mannitol may increase neurotoxicity because it allows greater delivery of anticancer drugs into the normal brain tissue than into the tumor tissues.

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Hypothalamic hamartoma

Report of two cases

Shunji Nishio, Shigeru Fujiwara, Yasutaka Aiko, Iwao Takeshita, and Masashi Fukui

✓ Two cases of hypothalamic hamartoma are presented. The first patient was a 4-year-old boy with precocious puberty, and the second was a 6-year-old boy with epileptic seizures. In both patients, clinical symptoms and signs appeared at the age of 2 years and progressed thereafter. Computerized tomography and magnetic resonance imaging in both cases disclosed a suprasellar mass lesion in continuity with the hypothalamus. Removal of the lesions affected the endocrinological status and/or seizure control. Pathological examination revealed the lesions to be composed of well-differentiated neuronal and glial cells. Immunohistochemical study demonstrated the presence of beta-endorphin, corticotropin-releasing factor, oxytocin, and neurofilament protein (210 kD) in the neuronal cells of the first patient, but no neuropeptides were detected in the second. Electron microscopic examination on the second patient disclosed the presence of many nonmyelinated and some myelinated neuronal processes containing dense-core and clear vesicles. The morphological characteristics and the role of surgery for this lesion are discussed.

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Satoshi Suzuki, Junichi Omagari, Shunji Nishio, Eiichiro Nishiye, and Masashi Fukui

Object. The authors assessed the efficacy of gamma knife radiosurgery (GKS) in the treatment of patients with 10 or more simultaneous metastatic brain tumors.

Methods. Gamma knife radiosurgery was performed for the treatment of 10 or more simultaneous metastatic brain tumors in 24 patients. The performance status before and after GKS was expressed using the Karnofsky Performance Scale (KPS). The cumulative survival rate was analyzed using the Kaplan—Meier method. The level of satisfaction with the procedure was assessed by telephone interview.

No patient has died due to brain metastasis—related symptoms, and all patients and/or their families were satisfied with the GKS. In 12 patients who had brain metastasis—related symptoms, five improved, six were unchanged, and one deteriorated, as reflected by the KPS scores. The cumulative survival rate calculated by the Kaplan—Meier method was 70.4%, 49.3%, and 12.3% at 12 weeks, 24 weeks, and 36 weeks, respectively. The median survival time was 11 weeks.

Conclusions. Single-fraction GKS can achieve acceptable tumor control, low morbidity, and good quality of life in the treatment of multiple metastatic brain tumors even in cases with 10 or more simultaneous metastases.

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Koji Yoshimoto, Shunji Nishio, Satoshi Suzuki, Masashi Fukui, and Kanehiro Hasuo

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Kazunari Oka, Hiroko Tsuda, Kazufumi Kamikaseda, Ryuji Nakamura, Masashi Fukui, Youko Nouzuka, and Katsuo Sueishi

✓ The physical act of operating on 13 patients with meningiomas was studied for its effect on the fibrinolytic system. Fibrinolytic abnormalities, mainly due to an increase of plasma fibrinolytic activity, appeared in three patients prior to, during, or after surgery. These patients demonstrated hemorrhagic diathesis in the operative wounds which was associated with a consumptive coagulopathy, namely, an increase of fibrin/fibrinogen degradation product concentration and a decrease of fibrinogen concentration in plasma. Antiplasmin agents (gabexate and tranexamic acid) were effective in minimizing loss of blood during and after the operation. Abnormal hyperfibrinolysis seems to play a role in hemostatic difficulties in patients undergoing surgery for meningioma.

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Toshio Matsushima, Tooru Inoue, Takanori Inamura, Yoshihiro Natori, Kiyonobu Ikezaki, and Masashi Fukui

Object. The purpose of the present study was to refine the transcerebellomedullary fissure approach to the fourth ventricle and to clarify the optimal method of dissecting the fissure to obtain an appropriate operative view without splitting the inferior vermis.

Methods. The authors studied the microsurgical anatomy by using formalin-fixed specimens to determine the most appropriate method of dissecting the cerebellomedullary fissure. While dissecting the spaces around the tonsils and making incisions in the ventricle roof, the procedures used to expose each ventricle wall were studied. Based on their findings, the authors adopted the best approach for use in 19 cases of fourth ventricle tumor.

The fissure was further separated into two slit spaces on each side: namely the uvulotonsillar and medullotonsillar spaces. The floor of the fissure was composed of the tela choroidea, inferior medullary velum, and lateral recess, which form the ventricle roof. In this approach, the authors first dissected the spaces around the tonsils and then incised the taenia with or without the posterior margin of the lateral recess. These precise dissections allowed for easy retraction of the tonsil(s) and uvula and provided a sufficient view of the ventricle wall such that the deep aqueductal region and the lateral region around the lateral recess could be seen without splitting the vermis. The dissecting method could be divided into three different types, including extensive (aqueduct), lateral wall, and lateral recess, depending on the location of the ventricle wall and the extent of surgical exposure required.

Conclusions. When the fissure is appropriately and completely opened, the approach provides a sufficient operative view without splitting the vermis. Two key principles of this opening method are sufficient dissection of the spaces around the tonsil(s) and an incision of the appropriate portions of the ventricle roof. The taenia(e) with or without the posterior margin of the lateral recess(es) should be incised.