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Kazunari Yoshida and Takeshi Kawase

Object. Since 1974, 27 patients with trigeminal neurinomas (TNs) have been treated at Keio University Hospital and ancillary institutes. In the present study the clinical features and developmental patterns of these 27 cases are analyzed, and the clinical features of 402 cases reported in the literature are reviewed. Based on the analysis of the developmental patterns of the TNs, the surgical strategy for a one-stage removal of TNs involving multiple fossae is described.

Methods. Trigeminal neurinomas are classified into six types according to tumor location. Types M, P, and E are tumors involving a single compartment, that is, the middle fossa, posterior fossa, or extracranial space, respectively. Types MP (middle and posterior fossae), ME (middle fossa and extracranial space), or MPE (middle and posterior fossae and extracranial space) are tumors involving multiple compartments. Advances in neuroimaging technologies, such as magnetic resonance imaging, have revealed a high incidence of TNs extending into multiple fossae, namely 36.2% in cases reported since 1983 and 59% in the authors' series. All but one of the most recent 19 patients in this series underwent skull base surgery, whereas the remaining nine patients were surgically treated via the conventional subdural approach. The rate of total tumor removal and the clinical outcome were significantly better in those patients treated by skull base surgery than those treated by conventional surgery.

Conclusions. The TNs extending into multiple fossae can be totally removed using the following single-stage surgical techniques: Type MP by the anterior transpetrosal approach; Type ME by the zygomatic or orbitozygomatic infratemporal approach; and Type MPE by the zygomatic transpetrosal approach. In 12 of 13 cases involving multiple fossae in this series, total tumor removal was achieved using single-stage skull base surgery.

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Takeshi Kawase, Shigeo Toya, Ryuzo Shiobara and Toru Mine

✓ Extradural subtemporal access to the petrosal ridge and a resection of the anterior pyramidal bone produced direct observation of the lower basilar artery, with minimum retraction of the temporal lobe and preservation of the temporal bridging veins. Two patients, with lower basilar trunk aneurysms facing toward the brain stem, were operated on by the “transpetrosal approach,” with successful clipping of the aneurysms. Auditory function was preserved in one case. This approach decreases the possibility of retraction damage to the temporal lobe, brain stem, or cranial nerves, and may be helpful for surgery of aneurysms arising around the vertebrobasilar junction or at the origin of the anterior inferior cerebellar artery.

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Kazuhide Adachi, Takeshi Kawase, Kazunari Yoshida, Takahito Yazaki and Satoshi Onozuka

Object

Surgery for skull base meningiomas (SBMs) can lead to complications because these lesions are difficult to approach and can involve cranial nerves and arteries. The authors propose a scoring system to evaluate the relative risks and benefits of surgical treatment of SBMs.

Methods

The authors used a 2-step process to construct their scale. First, they derived significant predictive variables from retrospective data on 132 SBM cases treated surgically (primary surgeries only) between May 2000 and December 2005. Next, they validated the predictive accuracy of their scoring system in 60 consecutive cases treated surgically between January 1995 and April 2000, including both primary and repeated surgeries. Finally, they investigated the effect of the surgery on the patients' preoperative symptoms for consecutive cases treated surgically between January 1995 and December 2005, including both primary surgeries and retreatments.

Results

Five items that predicted surgical risk were identified: 1) tumor attachment size; 2) arterial involvement; 3) brainstem contact; 4) central cavity location; and 5) cranial nerve group involvement. The authors named their scoring system the ABC Surgical Risk Scale, after the initial letters of these items. Each factor was assigned a score of 0–2 points, and an additional point was added for previous surgical treatment or for radiation, giving a possible total score of 12 points. On average, the scoring system allocated 2 points for gross-total resections, 6.1 points for near-total resections, and 9 points for subtotal resections, with significant differences between groups. For cases scoring ≥ 8 points, the percentage of cases showing neurological deterioration postoperatively exceeded the percentage showing improvement.

Conclusions

The authors conclude that this scoring system can be used to predict the extent of tumor removal and that the scores reflect the surgical risk.

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Raita Fukaya, Kazunari Yoshida, Takenori Akiyama and Takeshi Kawase

The origin of moyamoya disease remains unknown. The onset of the angiographically apparent changes of typical moyamoya disease occurs in childhood, but de novo development of the disease has not been confirmed angiographically. The authors report on a case of de novo development of moyamoya disease in a middle-aged female whose cerebral angiography demonstrated no abnormal findings 5 years previously. To the best of the authors' knowledge, this case is the first reported instance of de novo development of definite moyamoya disease verified angiographically. This case demonstrates that the de novo development of moyamoya disease in a middle-aged adult did in fact occur, and angiographically visible features of the disease took < 5 years to complete.

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Satoshi Takahashi, Yuichi Hirose, Eiji Ikeda, Raita Fukaya and Takeshi Kawase

✓The authors describe the case of a patient with a glioblastoma multiforme who showed remarkably good response to chemotherapy. A genetic analysis using comparative genomic hybridization (CGH) revealed that the tumor had a gain on the q arm of chromosome 1 (1q). Using CGH for a series of genetic analyses of more than 180 patients with gliomas, six were found to have a demonstrated 1q gain. Although the tumors in all six of these cases were histopathologically diagnosed as high-grade gliomas, compared with other malignant gliomas they demonstrated a good prognosis because of their favorable chemotherapeutic sensitivity. In immunohistochemical tests, most of the tumor cells in these cases were negative for O6-methylguanine–DNA methyltransferase, which antagonizes the effect of DNA-alkylating chemotherapeutic agents. The authors believed that a gain of 1q could be produced through the genetic events that cause loss of 1p, because these chromosomal aberrations have an imbalance of DNA copy number in common (1p <1q). A gain of 1q is an infrequent chromosomal aberration and its clinical importance should be investigated in a larger study; however, patients with malignant gliomas demonstrating a 1q gain possibly show longer survival and good response to chemotherapy similar to patients with tumors demonstrating 1p loss. The importance of using genetic analysis for gliomas is emphasized in this report because it may help in selecting cases responsive to chemotherapy and because appropriate treatment for these patients will lead to progress in the treatment of malignant gliomas.

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Shigeo Toya, Takeshi Kawase, Youichi Iisaka, Takanobu Iwata, Toshio Aki and Tsuneo Nakamura

✓ The effect of laser radiation on the central nervous system has been studied in cases of clinical and experimental tumors. However, no report yet exists on the effects of laser radiation on the cerebral microcirculation in vivo. Cerebral fluorescein angiography permits observations of small vessels that are not possible by conventional angiography. In this study, disturbance in the epicerebral microcirculation after carbon dioxide laser radiation was localized. On fluorescein angiograms, a circular zone of nonfilling of fluorescein dye around the site of impact, 1 to 1.5 mm in diameter, was seen throughout from the arterial to late venous phase. Around the nonfilling area, thrombus formation in small vessels and extravasation of the dye were demonstrated. Such extravasation of the fluorescein remained after the dye had faded from the venules and veins. Microscopically, coagulation necrosis was observed to coincide with the area of nonfilling of fluorescein dye in the fluorescein angiograms. In areas surrounding this, edema, dilatation or rupture of the capillaries, and thrombus formation in the arterioles were observed. Such areas coincided with those of extravasation of the fluorescein dye.

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Shigeo Ohba, Yuichi Hirose, Kazunari Yoshida, Takahito Yazaki and Takeshi Kawase

Object

The introduction of temozolomide (TMZ) has advanced chemotherapy for malignant gliomas. A considerable number of glioblastoma cases are refractory to TMZ, however, and the development of novel chemotherapeutic regimens is needed. The authors of previous studies have revealed that hsp90 is expressed at higher levels in human neoplastic tissues, including gliomas, than in normal tissues. Heat shock protein 90 is involved in a cytoprotective mechanism against cellular stressors such as DNA damage, and the authors hypothesized that hsp90 inhibitors might act as antitumor agents against gliomas and potentiate the cytotoxicity of DNA-damaging agents.

Methods

The authors examined the cytotoxicity of an hsp90 inhibitor, 17-(allylamino)-17-demethoxygeldanamycin (17-AAG), both alone and in combination with 1 of 3 DNA-damaging agents (cisplatin, 1,3-bis(2-chloroethyl)-1-nitrosourea, and TMZ) in human glioma cell lines. The cytotoxicity of these agents to glioma cells was measured using a colony formation assay. The cell cycle phase distribution, protein expression, and number of apoptotic cells were measured using a fluorescence-activated cell sorting assay, immunoblot assays, and double staining with annexin V and propidium iodide. In an in vivo experiment, 17-AAG, cisplatin, or 17-AAG and cisplatin were administered intraperitoneally to mice with xenografted U87MG cells, and the resulting tumor volumes were measured.

Results

The authors found that 17-AAG reduced the clonogenicity of U87MG cells, and at a low concentration (< 100 nM) potentiated the cytotoxicity of the DNA-crosslinking agents cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea, but not that of the DNA-methylating agent TMZ. This 17-AAG–induced potentiation of DNA crosslinking agent–induced cytotoxicity was a consequence of prolonged G2-M arrest accompanied by the suppression of cdc2 and cdc25C and of increased apoptotic cell death accompanied by the degradation of the antiapoptosis proteins Akt and survivin. Similar effects were observed when cells were treated with radicicol, another hsp90 inhibitor. The 17-AAG–induced enhancement of DNA crosslinking agent–induced cytotoxicity was also observed in other cell lines. In addition, 17-AAG sensitized xenografted U87MG cells to cisplatin in nude mice.

Conclusions

Heat shock protein 90–targeted therapy may be an effective strategy for potentiating chemotherapy using DNA-crosslinking agents for TMZ-refractory gliomas.

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Shigeo Ohba, Kazunari Yoshida, Yuichi Hirose, Eiji Ikeda, Yoichi Nakazato and Takeshi Kawase

This 32-year-old woman, 27 weeks pregnant, harbored a cystic mass with a solid component in the left frontal lobe. Histologically, the lesion was hypercellular and contained a diffuse sheet of eosinophilic cells of various sizes. The cells were almost round and had a few prominent, eccentrically placed, hyperchromatic nuclei of various sizes. Immunohistochemically, the tumor was reactive for vimentin, epithelial membrane antigen, cytokeratin AE1/AE3, smooth muscle actin, and BAF47/INI-1, and negative for glial fibrillary acidic protein, neurofilament protein, S100 protein, CK7, CK20, HMB-45, MIC2, and Bcl-2. The Ki 67 labeling index was 4.2%. Comparative genomic hybridization analysis revealed aberrations of the chromosomal copy number of +7 and −10. This tumor could not be categorized according to the present World Health Organization classification. Results of staining with glial fibrillary acidic protein were not consistent with a glioma, and staining with INI-1 was inconsistent with atypical teratoid/rhabdoid tumor. The tumor was therefore designated as a “cerebral tumor with extensive rhabdoid features.”

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Mami Ishikawa, Takayuki Ohira, Jun Namiki, Masato Kobayashi, Moriichiro Takase, Takeshi Kawase and Shigeo Toya

✓ In patients with hemifacial spasm, it has been said that the spasm is due to cross compression of the facial nerve by a blood vessel and that microvascular decompression (MVD) of the facial nerve is an effective treatment. The F waves, which result from backfiring of antidromically activated motor neurons of the facial motor nucleus, are indices of the excitability of the facial motor nucleus and are enhanced in patients with hemifacial spasm. Measuring blink reflexes and abnormal muscle responses (lateral spread), a characteristic sign of hemifacial spasm, has been used to investigate the mechanism of hemifacial spasm pathophysiologically. Thus the authors measured F waves of the facial muscle, blink reflexes, and abnormal muscle responses before and after MVD in patients suffering from hemifacial spasm to investigate the excitability of the facial motor nucleus and the course of the cure of hemifacial spasm after MVD. The authors obtained facial nerve—evoked electromyograms in 20 patients with hemifacial spasm before and after the MVD procedure. On the spasm side, the F waves and blink reflexes were enhanced preoperatively compared to those on the normal side and abnormal muscle responses were recorded in all patients. In 12 patients whose hemifacial spasm had not disappeared completely for 5.1 ± 1.7 (mean ± standard error) months following the MVD procedure, F waves were still enhanced significantly and abnormal muscle responses were still recordable, albeit at lower amplitude. Within 1 month after the hemifacial spasm had disappeared completely, F waves were still significantly enhanced in 17 patients and abnormal muscle responses were recorded in seven of 15 patients. Subsequently, the enhanced F waves and abnormal muscle responses disappeared completely. The authors' study supports the hypothesis that the cause of hemifacial spasm is hyperexcitability of the facial motor nucleus and suggests that additional surgery should not be performed for at least 2 years after MVD, because that period is necessary for the disappearance of the hyperexcitability of the facial motor nucleus.

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Hideki Murakami, Yuichi Hirose, Masachika Sagoh, Kazuhiro Shimizu, Masaru Kojima, Kazuhiro Gotoh, Yutaka Mine, Takuro Hayashi and Takeshi Kawase

Object. Thrombomodulin is a thrombin receptor on vascular endothelial cells that is highly expressed when these cells are injured, and it has anticoagulating activity. The authors investigated thrombomodulin expression to clarify why chronic subdural hematomas (CSDHs) continue to grow slowly, like a tumor, and are liquefied.

Methods. Burr hole craniotomy and drainage were performed in all 35 patients with CSDH who were included in the study. The plasma-soluble thrombomodulin and blood clotting factor values were determined in the hematoma and in peripheral blood. In the seven most recent cases, the plasma-soluble thrombomodulin values were determined in the residual hematoma collected from the drainage tube the day after surgery. The outer membranes of the CSDH that were obtained as specimens at operation were stained with monoclonal antibody against thrombomodulin for immunohistochemical studies. The plasma-soluble thrombomodulin values were higher (p < 0.0001), and conversely the values for factors V and VIII were lower in the hematoma than in peripheral blood (p < 0.0001). The plasma-soluble thrombomodulin values were lower in the residual hematomas than in the same lesions at operation (p = 0.018). The endothelial cells on the sinusoidal vessels exhibited immunoreactivity with thrombomodulin antibody in 28 (93%) of 30 cases.

Conclusions. The thrombomodulin is expressed on the sinusoidal vessels, and the blood coagulation system is inhibited in the hematoma. These findings indicate that these vessels are continuously injured and fail to heal. As a result, the bleeding from the sinusoidal vessels may persist, and the hematoma may grow slowly and fail to coagulate. It is suspected that transmitted pulsation variations in the hematoma cavity generate sinusoidal vessel injury.