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Analysis of the intercavernous sinus in sellar lesions using multidetector computed tomography digital subtraction venography.

Mizutani K, Toda M, Yoshida K

World Neurosurg pii: S1878-8750(15)01095-5. 2015年09月

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Upfront chemotherapy and subsequent resection for molecularly defined gliomas

Sasaki Hikaru, Hirose Yuichi, Yazaki Takahito, Kitamura Yohei, Katayama Makoto, Kimura Tokuhiro, Fujiwara Hirokazu, Toda Masahiro, Ohira Takayuki, Yoshida Kazunari

Journal of Neuro-Oncology 124 （ 1 ） 127 - 135 2015年08月

ISSN 0167-594X

Functional preservation is critical in glioma surgery, and the extent of resection influences survival outcome. Neoadjuvant chemotherapy is a promising option because of its potential to facilitate tumor shrinkage and maximum tumor resection. The object of this study was to assess the utility of the neoadjuvant strategy in a prospective series of gliomas with favorable molecular status. Twenty-six consecutive cases of diffuse gliomas of WHO grade II or III with either 1p19q codeletion or MGMT methylation were treated with upfront chemotherapy following maximal safe removal. In cases of incomplete initial surgery, second-look resection was intended after tumor volume decrease by chemotherapy. Among 22 evaluable cases, chemotherapy led to a median change in the sum of the product of perpendicular diameters of −35 %, and 14 out of the 22 cases (64 %) showed objective response. Second-look resection after tumor volume decrease was performed in 12 out of 19 cases of incomplete initial surgery (GTR/STR 9, removal of residual methionine PET uptake 3). The median progression-free survival among the 22 patients with grade II tumors was 57 months, with some cases showing durable progression-free survival after second-look resection. MIB-1 indices of the second-look resected tumors were lower than those of the initial tumors, and the methylation status of the MGMT gene was unchanged. Neoadjuvant chemotherapy based on molecular guidance often produces significant volume decrease of incompletely resected gliomas. Radical second-look resection is an optional advantage of upfront chemotherapy for chemosensitive gliomas compared with initial radiotherapy.

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Steroid psychosis caused by perioperative steroid replacement for pituitary adenoma

Mizutani Katsuhiro, Toda Masahiro, Kikuchi Ryogo, Uchida Hiroyuki, Yoshida Kazunari

Keio Journal of Medicine 64 （ 1 ） 11 - 15 2015年03月

ISSN 0022-9717

Steroid psychosis is a frequent complication of steroid treatment. Although perioperative steroid replacement therapy is generally administered in patients undergoing pituitary surgery, there are no previous reports concerning the development of steroid psychosis after perioperative steroid replacement therapy following pituitary surgery. We herein report a case of steroid psychosis induced by perioperative steroid replacement therapy for pituitary surgery. A 35-year-old man presented with a visual disturbance that had persisted for 1 year. A magnetic resonance imaging scan showed a large pituitary tumor, and a laboratory study revealed slight dysfunction of the hypothalamo-pituitary-adrenal axis. The patient was diagnosed with a non-functioning pituitary tumor and underwent tumor resection via the endoscopic endonasal approach. The initial dose of perioperative steroid replacement therapy was 200 mg of hydrocortisone administered immediately before the operation. The replacement dose was gradually tapered and discontinued over a 7-day period. On postoperative day 4, the patient exhibited an elated mood, grandiose delusions, anxiety, and agitation. We diagnosed these psychiatric symptoms as steroid psychosis induced by steroid replacement and we prescribed risperidone as a treatment. The symptoms gradually improved and did not recur. This case highlights the risk of steroid psychosis following treatment with perioperative steroid replacement therapy for pituitary adenoma and raises questions regarding the appropriateness of perioperative steroid replacement for pituitary adenoma.

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Grüber's ligament as a useful landmark for the abducens nerve in the transnasal approach

Tomio Ryosuke, Toda Masahiro, Sutiono Agung B udi, Horiguchi Takashi, Aiso Sadakazu, Yoshida Kazunari

Journal of neurosurgery 122 （ 3 ） 499 - 503 2015年03月

OBJECT: Extended endoscopic transnasal surgeries for skull base lesions have recently been performed. Some expert surgeons have attempted to remove tumors such as chordomas, meningiomas, and pituitary adenomas in the clival region using the transnasal approach and have reported abducens nerve injury as a common complication. There have been many microsurgical anatomical studies of the abducens nerve, but none of these studies has described an anatomical landmark of the abducens nerve in the transnasal approach. In this study the authors used cadaver dissections to describe Grüber's ligament as the most reliable landmark of the abducens nerve in the transnasal transclival view.METHODS: The petroclival segment of the abducens nerve was dissected in the interdural space-which is also called Dorello's canal, the petroclival venous gulf, or the sphenopetroclival venous confluence-using the transnasal approach in 20 specimens obtained from 10 adult cadaveric heads.RESULTS: The petroclival segment of the abducens nerve clearly crossed and attached to Grüber's ligament in the interdural space, as noted in the transnasal view. The average length of the dural porus to the intersection on the abducens nerve was 5.2 ± 1.0 mm. The length of the posterior clinoid process (PCP) to the intersection on Grüber's ligament was 6.4 ± 2.6 mm. The average width of Grüber's ligament at the midsection was 1.6 ± 0.5 mm.CONCLUSIONS: Grüber's ligament is considered a useful landmark, and it is visible in most adults. Thus, surgeons can find the abducens nerve safely by visualizing inferolaterally along Grüber's ligament from the PCP.

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Petrous apex cholesterol granuloma

Shibao Shunsuke, Toda Masahiro, Tomita Toshiki, Saito Katsuya, Ogawa Kaoru, Kawase Takeshi, Yoshida Kazunari

Neurologia Medico-Chirurgica 55 （ 4 ） 351 - 355 2015年

ISSN 0470-8105

Recently, petrous apex cholesterol granulomas (CGs) have been treated via the endoscopic endonasal transsphenoidal approach (EEA) using a silicone tube, to prevent drainage route occlusion. Occlusion of the drainage route has led to problems with recurrence. The aim of this report is to describe the use of a surgical technique to prevent drainage route occlusion. In surgical technique, the posterolateral wall of the sphenoid sinus was opened by EEA. After cyst debridement, a vascularized nasoseptal flap with a width of approximately 4 cm was inserted into the lumen with a silicone T-tube with a diameter of 7 mm. This technique was used in two patients: the first patient during the second operation after recurrence following occlusion of the drainage route, and the second patient during the first operation. Opening of the cyst wall was confirmed endoscopically in both patients 12–24 months after surgery, even after removal of the T-tube. In conclusion, the use of a pedicled nasoseptal flap with a silicone tube is useful to prevent CG recurrence, by paranasal cavitization of the cystic cavity.

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Analysis of the intercavernous sinuses using multidetector computed tomography digital subtraction venography (CT-DSV)

Mizutani Katsuhiro, Toda Masahiro, Yoshida Kazunari

Clinical Neurology and Neurosurgery 131 31 - 34 2015年

ISSN 0303-8467

Purposes The intercavernous sinuses (ICSs) connect both sides of the cavernous sinus. Knowledge of the ICSs is useful when employing the endoscopic endonasal transsphenoidal approach. Although there were some studies concerning the anatomy of ICSs using cadavers, there is no well-recognized method of the radiological evaluation of the ICSs. Therefore, we evaluate the ICSs using computed tomography digital subtraction venography (CT-DSV) in the cases of unruptured aneurysm that had the normal sellae anatomy. Methods We retrospectively analyzed 97 cases of unruptured cerebral aneurysm that had normal parasellar and sellar anatomy except for the aneurysms. The analysis was performed using the multi-planar reconstruction images obtained by CT-DSV in these cases. Results The anterior ICS (AICS), inferior ICS (IICS) and posterior ICS (PICS) were detected in 51 cases (52.6%), 28 cases (28.9%) and 76 cases (78.4%) respectively. In the cases older than 51 years old, the AICS was detected significantly less often than in those younger than 50 years old. Conclusions The CT-DSV images directly reflected the blood flow. Most of the past research on the ICSs was obtained using cadavers, which could therefore not directly assess the normal human blood flow. The present study showed the usefulness of CT-DSV for evaluating the ICSs and to understand the normal anatomy of the ICSs.

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GH-producing Pituitary Adenoma and Concomitant Rathke’s Cleft Cyst: A case report and short review.

Tamura R, Takahashi S, Emoto K, Nagashima H, Toda M, Yoshida K

Case Rep Neurol Med 2015 948025 2015年

研究論文（学術雑誌）, 共著

Transoral vs. endoscopic endonasal approach for clival/upper cervical chordoma

Shidoh Satoka, Toda Masahiro, Kawase Takeshi, Nakajima Hideo, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Neurologia Medico-Chirurgica 54 （ 12 ） 991 - 998 2014年12月

ISSN 0470-8105

The surgical results of 18 cases of clival/upper cervical chordoma treated in the last decade via the endoscopic endonasal approach (EEA, 9 cases) and the transoral-transpalatal approach (TO-TPA, 9 cases) were compared. Each group showed the same incidence of subdural invasion, with 5 cases each. The superior (frontal base) and lateral surgical fields were wider by EEA, but the inferior view lower than the cranio-vertebral junction (CVJ) was wider by TO-TPA. Gross total removal was achieved in 3 cases in the EEA group, but in only 1 case in the TO-TPA group. Differences in radicality might be due to the extent of the lateral and subdural overview. However for large tumors extending below the CVJ, TO-TPA was the only viable approach for surgical removal. Surgical complications were higher in the EEA (4 cases) than the TO-TPA group (1 case), and were mainly caused by aggressive management of subdural invasion in the EEA group. Post-operative oral intake was earlier and the operative time was shorter in the EEA group. The surgical results were more radical and less invasive in the EEA group than the TO-TPA group. However in tumors extending below the CVJ, the surgical field in EEA was limited, indicating the need to use the transoral route or a combination of routes. A higher complication rate following subdural management was a negative factor that requires improvement in the EEA group and two-staged EEA followed by a transcranial approach may be considered for the cases with subdural invasion.

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Analysis of the bacterial flora in the nasal cavity and the sphenoid sinus mucosa in patients operated on with an endoscopic endonasal transsphenoidal approach

Shibao Shunsuke, Toda Masahiro, Tomita Toshiki, Ogawa Kaoru, Yoshida Kazunari

Neurologia Medico-Chirurgica 54 （ 12 ） 1009 - 1013 2014年12月

ISSN 0470-8105

The aim of this study was to analyze the bacterial flora in the nasal cavity and sphenoid sinus and evaluate the sensitivity of these bacteria to antibiotics that can be used to prevent postoperative meningitis. Bacteria of the preoperative nasal cavity and intraoperative sphenoid sinus mucosa were cultured and analyzed in 40 patients (20 men and 20 women; mean age, 52.2 years) who underwent endoscopic transsphenoidal surgery. The sensitivity of these bacteria to cephalosporin, a representative prophylactic antibiotic, was examined. Staphylococcus epidermidis was the most frequently detected species in both spaces; 24 (38.7%) of 62 isolates in the nasal cavity and 26 (37.1%) of 70 isolates in the sphenoid sinus. In contrast, Corynebacterium species were found mainly in the nasal cavity, and anaerobic bacteria were found only in the sphenoid sinus. Bacteria that were resistant to cephalosporin were found in the nasal cavity in 3.2% of patients and in the sphenoid sinus in 20% of patients. In conclusion, the composition of bacterial flora, including bacteria that are resistant to prophylactic antibiotics, differs between the nasal cavity and the sphenoid sinus.

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Functional analysis of a novel glioma antigen, EFTUD1

Saito Katsuya, Iizuka Yukihiko, Ohta Shigeki, Takahashi Satoshi, Nakamura Kenta, Saya Hideyuki, Yoshida Kazunari, Kawakami Yutaka, Toda Masahiro

Neuro-Oncology 16 （ 12 ） 1618 - 1629 2014年12月

ISSN 1522-8517

BACKGROUND: A cDNA library made from 2 glioma cell lines, U87MG and T98G, was screened by serological identification of antigens by recombinant cDNA expression (SEREX) using serum from a glioblastoma patient. Elongation factor Tu GTP binding domain containing protein 1 (EFTUD1), which is required for ribosome biogenesis, was identified. A cancer microarray database showed overexpression of EFTUD1 in gliomas, suggesting that EFTUD1 is a candidate molecular target for gliomas.METHODS: EFTUD1 expression in glioma cell lines and glioma tissue was assessed by Western blot, quantitative PCR, and immunohistochemistry. The effect on ribosome biogenesis, cell growth, cell cycle, and induction of apoptosis and autophagy in glioma cells during the downregulation of EFTUD1 was investigated. To reveal the role of autophagy, the autophagy-blocker, chloroquine (CQ), was used in glioma cells downregulating EFTUD1. The effect of combining CQ with EFTUD1 inhibition in glioma cells was analyzed.RESULTS: EFTUD1 expression in glioma cell lines and tissue was higher than in normal brain tissue. Downregulating EFTUD1 induced G1 cell-cycle arrest and apoptosis, leading to reduced glioma cell proliferation. The mechanism underlying this antitumor effect was impaired ribosome biogenesis via EFTUD1 inhibition. Additionally, protective autophagy was induced by glioma cells as an adaptive response to EFTUD1 inhibition. The antitumor effect induced by the combined treatment was significantly higher than that of either EFTUD1 inhibition or CQ alone.CONCLUSION: These results suggest that EFTUD1 represents a novel therapeutic target and that the combination of EFTUD1 inhibition with autophagy blockade may be effective in the treatment of gliomas.

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Pilocytic astrocytoma with anaplastic features presenting good long-term clinical course after surgery alone

Saito Katsuya, Toda Masahiro, Yoshida Kazunari

Child's Nervous System 2014年08月

ISSN 0256-7040

Purpose Pilocytic astrocytomas (PAs) are the most common brain tumor in children and typically have an excellent prognosis. However, some PAs show histologically anaplastic features. It is reported that PAs with anaplastic features often need the postoperative radiation and chemotherapy due to aggressiveness such as early local recurrence and dissemination. We describe an interesting case of primary anaplastic PA with good clinical course in the long-term. Methods A 10-year-old man presented with worsening headache and vomiting. Magnetic resonance imaging (MRI) showed a large cystic tumor with contrast-enhanced solid component in a right occipital lobe. Magnetic resonance spectroscopy (MRS) showed the decrease of N-acetylaspartate (NAA) and the increase of choline and lipids, which suggested the malignancy. Results The patient was operated with an occipital lobectomy. The tumor was incompletely resected due to the deep invasion to the inner wall of lateral ventricle. Pathological diagnosis was a pilocystic astrocytoma with anaplastic features. Although aggressive features were suspected from magnetic resonance spectroscopy and pathological findings, the remnant tumor showed no recurrence for 8 years without any postoperative treatments. Conclusion PAs could exhibit variable behavior, and careful managements including wait-and-scan should be considered, because adjuvant therapies may cause child's growth disorder and malignant transformation. © 2014 Springer-Verlag Berlin Heidelberg.

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Primary dural closure and anterior cranial base reconstruction using pericranial and nasoseptal multi-layered flaps in endoscopic-assisted skull base surgery

Tomio Ryosuke, Toda Masahiro, Tomita Toshiki, Yazawa Masaki, Kono Maya, Ogawa Kaoru, Yoshida Kazunari

Acta Neurochirurgica 156 （ 10 ） 1911 - 1915 2014年

ISSN 0001-6268

Introduction: Dural and anterior cranial base reconstruction is essential in the surgical resection of a craniofacial tumor that extends from the paranasal sinuses to the subdural space. Watertight reconstruction of vascularized tissue is essential to prevent postoperative liquorrhea, especially under conditions that prevent wound healing (e.g., postoperative irradiation therapy).Method: We successfully treated two cases of olfactory neuroblastoma by endoscopic-assisted craniotomy with primary dural closure and anterior cranial base reconstruction using a multi-layered flap technique. Dural defects were closed using temporal fascia or fascia lata in a conventional fashion, immediately after detaching the subdural tumor, in order to isolate and prevent contamination of subdural components and cerebrospinal fluid (CSF) from the tumor and nasal sinuses. Tumor removal and anterior cranial base reconstruction were performed without any concern of CSF contamination after dural closure by craniotomy and endoscopic endonasal approach (EEA). Vascularized pericranial flaps (PCF) and nasoseptal flaps (NSF) were used simultaneously as doubled-over layers for reconstruction.Results: The tumor was completely removed macroscopically and the anterior cranial base was reconstructed in both cases. CSF leak and postoperative meningitis were absent. Postoperative and irradiation therapy courses were successful and uneventful.Conclusions: This multi-layered anterior cranial base reconstruction consisted of three layers: a fascia for dural plasty and double-layered PCF and NSF. This surgical reconstruction technique is suitable to treat craniofacial tumors extending into the subdural space through the anterior cranial base dura mater.

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Anterior petrosal approach

Tomio Ryosuke, Toda Masahiro, Yoshida Kazunari, Borghei-Razavi Hamid

Journal of Neurosurgery 120 （ 5 ） 1249 - 1250 2014年

ISSN 0022-3085

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Isolated Pituitary Tuberculoma - Case Reports –

Saito K, Toda M, Shido S, Tomita T, Ogawa K, Yoshida K.

NMC Case Report Journal 2013 （ 0330 ） 2014年

研究論文（学術雑誌）, 共著

Sox6 Up-Regulation by Macrophage Migration Inhibitory Factor Promotes Survival and Maintenance of Mouse Neural Stem/Progenitor Cells

Ohta Shigeki, Misawa Aya, Lefebvre Véronique, Okano Hideyuki, Kawakami Yutaka, Toda Masahiro

PLoS ONE 8 （ 9 ） 2013年09月

Macrophage migration inhibitory factor (MIF) has important roles in supporting the proliferation and/or survival of murine neural stem/progenitor cells (NSPCs), but downstream effectors remain unknown. We show here that MIF robustly increases the expression of Sox6 in NSPCs in vitro. During neural development, Sox6 is expressed in the ventricular zone of the ganglionic eminence (GE) of mouse brains at embryonic day 14.5 (E14.5), cultured NSPCs from E14.5 GE, and NSPCs in the subventricular zone (SVZ) around the lateral ventricle (LV) of the adult mouse forebrain. Retroviral overexpression of Sox6 in NSPCs increases the number of primary and secondary neurospheres and inhibits cell differentiation. This effect is accompanied with increased expression of Hes1 and Bcl-2 and Akt phosphorylation, thus suggesting a role for Sox6 in promoting cell survival and/or self-renewal ability. Constitutive activation of the transcription factor Stat3 results in up-regulation of Sox6 expression and chromatin immunoprecipitation analysis showed that MIF increases Stat3 binding to the Sox6 promoter in NSPCs, indicating that Stat3 stimulates Sox6 expression downstream of MIF. Finally, the ability of MIF to increase the number of primary and secondary neurospheres is inhibited by Sox6 gene silencing. Collectively, our data identify Sox6 as an important downstream effector of MIF signaling in stemness maintenance of NSPCs. © 2013 Ohta et al.

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Infratentorial low-grade oligoastrocytoma with aggressive clinical behavior in an adult

Sano Keisho, Toda Masahiro, Sasaki Hikaru, Kitamura Yohei, Mikami Shuji, Hirato Junko, Inoue Satoshi, Kawase Takeshi, Yoshida Kazunari

Brain Tumor Pathology 30 （ 2 ） 99 - 103 2013年04月

ISSN 1433-7398

Oligoastrocytoma preferentially arises in the cerebral hemisphere, and a cerebellar location is unusual. We report the case of a 35-year-old woman with an aggressive cerebellar tumor histopathologically diagnosed as oligoastrocytoma World Health Organization (WHO) grade II. After partial removal of the tumor, she underwent concomitant temozolomide (TMZ) therapy with local irradiation followed by additional TMZ monotherapy. However, her symptoms gradually worsened, and chronological magnetic resonance imaging showed remarkable tumor enlargement. In accordance with the aggressive clinical course, unfavorable genetic characteristics such as the gain of the entire chromosome 7, loss of 9p, absence of 1p/19q codeletion, absence of methylation of the O6- methylguanine-deoxyribonucleic acid methyltransferase promoter, and absence of the isocitrate dehydrogenase-1 mutation were observed. The present case illustrates that these molecular characteristics represent the biological features of gliomas more closely than the histopathological diagnosis and may also suggest that infratentorial gliomas arise through a distinct tumorigenic pathway from their supratentorial counterparts. © The Japan Society of Brain Tumor Pathology 2012.

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Our experience in anterior petrosal approach. Letter to the editor.

Tomio R, Borghei-Razavi H, Toda M, Yoshida K.

J Neurosurg 2013年

研究論文（学術雑誌）, 共著

Transoral-transpalatal approach and endoscopic endonasal approach for chordomas of the craniovertebral junction

Shidoh S, Toda M, Nakajima H, Tomita T, Ogawa K, Kawase T, Yoshida K

J Neurophysiol 4 （ 4 ） 162 2013年

研究論文（学術雑誌）, 共著, 査読有り

Macrophage migration inhibitory factor (MIF) promotes cell survival and proliferation of neural stem/progenitor cells

Ohta Shigeki, Misawa Aya, Fukaya Raita, Inoue Satoshi, Kanemura Yonehiro, Okano Hideyuki, Kawakami Yutaka, Toda Masahiro

Development (Cambridge) 139 （ 19 ） 2012年10月

ISSN 0950-1991

In a previous study, we showed that murine dendritic cells (DCs) can increase the number of neural stem/progenitor cells (NSPCs) in vitro and in vivo. In the present study, we identified macrophage migration inhibitory factor (MIF) as a novel factor that can support the proliferation and/or survival of NSPCs in vitro. MIF is secreted by DCs and NSPCs, and its function in the normal brain remains largely unknown. It was previously shown that in macrophages, MIF binds to a CD74-CD44 complex. In the present study, we observed the expression of MIF receptors in mouse ganglionic-eminence-derived neurospheres using flow cytometry in vitro. We also found CD74 expression in the ganglionic eminence of E14 mouse brains, suggesting that MIF plays a physiological role in vivo. MIF increased the number of primary and secondary neurospheres. By contrast, retrovirally expressed MIF shRNA and MIF inhibitor (ISO-1) suppressed primary and secondary neurosphere formation, as well as cell proliferation. In the neurospheres, MIF knockdown by shRNA increased caspase 3/7 activity, and MIF increased the phosphorylation of Akt, Erk, AMPK and Stat3 (Ser727), as well as expression of Hes3 and Egfr, the products of which are known to support cell survival, proliferation and/or maintenance of NSPCs. MIF also acted as a chemoattractant for NSPCs. These results show that MIF can induce NSPC proliferation and maintenance by multiple signaling pathways acting synergistically, and it may be a potential therapeutic factor, capable of activating NSPC, for the treatment of degenerative brain disorders. © 2012. Published by The Company of Biologists Ltd.

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Epidural anterior petrosectomy with subdural visualization of sphenobasal vein via the anterior transpetrosal approach-technical case report

Ichimura Shinya, Yoshida Kazunari, Kagami Hiroshi, Inaba Makoto, Orii Maaya, Kitamura Yohei, Saga Isako, Toda Masahiro

Neurosurgical Review 35 （ 4 ） 609 - 613 2012年10月

ISSN 0344-5607

The drainage of the superficialmiddle cerebral vein (SMCV) is classified into four subtypes. The sphenobasal vein (SBV) drains from the SMCV to the pterygoid venous plexus at the temporal skull base. Epidural procedures in the standard anterior transpetrosal approach (ATPA) may damage the route of the SBV. We report a case in which modified surgical procedures via the ATPA were used to preserve the SBV. A 45-year-old man complained of right facial pain. Magnetic resonance images revealed a right cerebellopontine tumor suggestive of an epidermoid cyst. Right carotid angiography revealed that the SMCV drained into the pterygoid venous plexus via the SBV. The convexity dura mater of the temporal lobe was cut and the anterior part of the temporal lobe was retracted subdurally. The SBV was visualized from the subdural side. The basal dura mater of the temporal lobe posterior to the SBV was cut and the posterior part of the temporal lobe was retracted epidurally. After dissecting the dura mater medial to the greater petrosal nerve and to the edge of the petrous apex, the petrous apex was exposed and drilled out without injuring the SBV. The superior petrous sinus and the tentorium were cut. The tumor compressed the root exit zone of the trigeminal nerve. The tumor was grossly totally removed. ThemodifiedATPA (epidural anterior petrosectomy with subdural visualization of the SBV) is effective in preserving the SBV. © Springer-Verlag 2012.

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