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Keisuke Maruyama, Kyousuke Kamada, Masahiro Shin, Daisuke Itoh, Yoshitaka Masutani, Kenji Ino, Masao Tago and Nobuhito Saito

Object

No definitive method of preventing visual field deficits after stereotactic radiosurgery for lesions near the optic radiation (OR) has been available so far. The authors report the results of integrating OR tractography based on diffusion tensor (DT) magnetic resonance imaging into simulated treatment planning for Gamma Knife surgery (GKS).

Methods

Data from imaging studies performed in 10 patients who underwent GKS for treatment of arteriovenous malformations (AVMs) located adjacent to the OR were used for the simulated treatment planning. Diffusion tensor images performed without the patient's head being secured by a stereotactic frame were used for DT tractography, and the OR was visualized by means of software developed by the authors. Data from stereotactic 3D imaging studies performed after frame fixation were coregistered with the data from DT tractography. The combined images were transferred to a GKS treatment-planning workstation. Delivered doses and distances between the treated lesions and the OR were analyzed and correlated with posttreatment neurological changes.

Results

In patients presenting with migraine with visual aura or occipital lobe epilepsy, the OR was located within 11 mm from AVMs. In a patient who developed new quadrantanopia after GKS, the OR had received 32 Gy. A maximum dose to the OR of less than 12 Gy did not cause new visual field deficits. A maximum dose to the OR of 8 Gy or more was significantly related to neurological change (p < 0.05), including visual field deficits and development or improvement of migraine.

Conclusions

Integration of OR tractography into GKS represents a promising tool for preventing GKS-induced visual disturbances and headaches. Single-session irradiation at a dose of 8 Gy or more was associated with neurological change.

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Keisuke Maruyama, Masahiro Shin, Masao Tago, Hiroki Kurita, Nobutaka Kawahara, Akio Morita and Nobuhito Saito

Object

Appropriate management of hemorrhage after Gamma Knife surgery (GKS) for arteriovenous malformations (AVMs) of the brain is poorly understood, although a certain proportion of patients suffer from hemorrhage.

Methods

Among 500 patients observed for 1 to 183 months (median 70 months) after GKS, 32 patients (6.4%) suffered a hemorrhage. Hemorrhage developed even after angiographically documented obliteration of the AVM in five (2%) of 250 patients followed for 1 to 133 months (median 75 months) post-GKS. These patients had been treated according to their pathological condition. Treatment of these patients and their outcomes were retrospectively reviewed. As a management strategy in patients with preobliteration hemorrhage, the intracerebral hematoma and the AVM nidus were removed in four patients, and chronic encapsulated hematoma was removed in three. Among 11 patients who were conservatively treated, AVMs were ultimately obliterated in five, including three patients who underwent repeated GKS. Intracerebral hematoma from angiographically documented obliterated AVMs was radically resected in two patients, including one who also underwent aspiration of an accompanying symptomatic cyst. Intraoperative bleeding was easily controlled in these patients. Outcomes after hemorrhage, measured with the modified Rankin Scale, were significantly better in patients with postobliteration hemorrhage than in those with preobliteration hemorrhage (p < 0.05).

Conclusions

Various types of hemorrhagic complications after GKS for AVMs can be properly managed based on an understanding of each pathological condition. Although a small risk of bleeding remains after angiographically demonstrated obliteration, surgery for such AVMs is safe, and the patient outcomes are more favorable. Radical resection to prevent further hemorrhage is recommended for ruptured AVMs after obliteration because such AVMs can cause repeated hemorrhages.

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Kyousuke Kamada, Tomoki Todo, Yoshitaka Masutani, Shigeki Aoki, Kenji Ino, R.T., Akio Morita and Nobuhito Saito

Object

There is continuous interest in the monitoring of language function during tumor resection around the fron-totemporal regions of the dominant hemisphere. The aim of this study was to visualize language-related subcortical connections, such as the arcuate fasciculus (AF) by diffusion tensor (DT) imaging–based tractography.

Methods

Twenty-two patients with brain lesions adjacent to the AF in the frontotemporal regions of the dominant hemisphere were studied. The AF tractography was accomplished by placing initiation and termination sites (seed and target points) in the frontal and temporal regions, which were functionally identified by using functional magnetic resonance (fMR) imaging in conjunction with a verb generation task and magnetoencephalography (MEG) in conjunction with a reading task. The combination of fMR imaging and MEG data clearly demonstrated the hemispheric dominance of language functions, which was confirmed by an intracranial amobarbital test (Wada procedure). In all 22 patients, the authors were able to consistently visualize the AF by DT imaging–based tractography, using the functionally identified seed and target points and a fractional anisotropy value of 0.16. In two of 22 cases investigated, the functional information, including the results of AF tractography, fMR imaging, and MEG, was imported to a neuronavigation system and was validated by bipolar electric stimulation of the cortical and subcortical areas during awake surgery. The cortical stimulation to the gyrus that included the area of activation identified in fMR imaging with the language task evoked speech arrest, while the subcortical stimulation close to the AF reproducibly caused paranomia without speech arrest. Postoperative AF tractography showed that the distances between the stimulus points and the AF were within 6 mm.

Conclusions

The combination of these techniques facilitated accurate identification of the location of the AF and verification of the language fibers.

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Nobutaka Kawahara, Tomio Sasaki, Takahiro Asakage, Kazunari Nakao, Masashi Sugasawa, Hirotaka Asato, Isao Koshima and Nobuhito Saito

Object

Primary temporal bone malignancy is a rare form of tumor for which the therapeutic strategy remains controversial. In this study, the authors reviewed their experience with radical temporal bone resection (TBR) of such lesions and analyzed the long-term results to provide treatment recommendations.

Methods

Between 1994 and 2006, 17 patients (10 men and 7 women) underwent total or subtotal TBR for primary temporal bone malignancies. Tumors were graded according to the University of Pittsburgh system. The effects of surgical margins and tumor extensions on patient survival were analyzed using the Kaplan–Meier method.

Results

All tumors, except 1, were graded T4 (most advanced). Subtotal TBR was performed in 14 patients, and total TBR was performed in 3. The surgical margin was tumor negative in 10 patients and tumor positive in 7. For large tumors extending into the infratemporal fossa or encroaching on the jugular foramen, orbitozygomatic (3 patients) and posterior transjugular (4 patients) approaches were combined with the standard approach, and en bloc resection with a negative margin was achieved in all cases but 1. The follow-up time ranged from 0.3–11.6 years (mean 3.3 years). The 5-year recurrence-free and disease-specific survival rates were 67.5 and 60.1%, respectively. When a negative surgical margin was achieved, the survival rates improved to 100 and 89%, respectively.

Conclusions

The neurosurgical skull base technique could improve the probability of en bloc resection with a tumor-free margin for extensive temporal bone malignancies, which would cure a subset of patients. The active participation of neurosurgeons would improve patient care in this field.

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Keisuke Maruyama, Tomoyuki Koga, Masahiro Shin, Hiroshi Igaki, Masao Tago and Nobuhito Saito

Object

Optimal timing of Gamma Knife surgery (GKS) after hemorrhage from brain arteriovenous malformations (AVMs) is unclear and of concern to neurosurgeons because GKS is usually performed after absorption of the hematoma. The authors investigated whether waiting for hematoma absorption is beneficial and aimed to clarify the optimal treatment timing.

Methods

The authors retrospectively studied 211 patients with AVMs who presented with hemorrhage and underwent GKS as the initial treatment. Patients were categorized into 3 groups according to the interval between the time of first hemorrhage and GKS, as follows: Group 1, 0–3 months (70 patients); Group 2, 3–6 months (62 patients); and Group 3, > 6 months (79 patients). The obliteration rates, number of hemorrhages before and after GKS, and complication rates were compared between these 3 groups. The authors also analyzed a subgroup of 127 patients who presented with intracerebral hemorrhage (ICH) to identify the influence of ICH on outcome.

Results

After a median follow-up of 6.3 years, the rates of obliteration, hemorrhage after treatment, and complication were not significantly different between the 3 groups even though the patients with a longer interval before GKS (Group 3) had more AVMs in eloquent areas and neurological deficits. However, the numbers of patients with preoperative hemorrhage in the interval before GKS was significantly higher in Group 3 (1, 3, and 20 patients in Group 1, 2, and 3, respectively). These results were similar in the analyses of 127 patients presenting with ICH.

Conclusions

No benefit was detected in waiting for hematoma absorption until GKS after hemorrhage from AVM. Because of higher hemorrhagic risk until GKS > 6 months after hemorrhage, the authors recommend GKS within 6 months after hemorrhage.

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Keisuke Takai, Taichi Kin, Hiroshi Oyama, Akira Iijima, Masaaki Shojima, Hajime Nishido and Nobuhito Saito

Object

Digital subtraction (DS) angiography is the gold standard for diagnosing spinal vascular malformations. Recently, multidetectorrow spiral CT and contrast-enhanced MR angiography have been introduced as screening examinations before DS angiography. These methods, however, do not always determine the accurate location of an arteriovenous shunt because the resulting images lack information about the spinal cord or the dura mater.

Methods

Between April 2009 and December 2010, 13 patients underwent imaging evaluations for spinal vascular malformations at the authors' university hospital. This group included 8 patients with spinal dural arteriovenous fistulas (AVFs), 3 with perimedullary AVFs, and 2 with intramedullary arteriovenous malformations. Using data from these patients, the authors attempted to develop 3D computer graphics (CG) based upon the fusion of 3D rotational angiography and postmyelographic CT. They subsequently verified the accuracy of this imaging method. Ten of these 13 patients underwent surgical treatment for their lesions (11 AVFs), and for these 11 lesions the authors compared the diagnoses obtained using 3D CG with those obtained using conventional DS angiography.

Results

In all 13 cases, 3D CG images of the spinal lesions were successfully developed using the patients' actual data. Four (36%) of 11 AVFs were correctly identified using DS angiography, whereas 10 (91%) were correctly identified using 3D CG. Results from 3D CG of spinal AVFs corresponded well with operative findings, and 3D CG was significantly better than conventional DS angiography at predicting AVF location (p = 0.024, Fisher exact test).

Conclusions

To the authors' knowledge, this is the first reported case series in which 3D CG of spinal vascular malformations was used to provide simultaneous, stereoscopic visualization of the spinal vascular system, spinal cord, dura mater, and bone. The 3D CG method provides precise visual images for the diagnosis and treatment of these lesions.

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Katsushige Watanabe, Takashi Watanabe, Akio Takahashi, Nobuhito Saito, Masafumi Hirato and Tomio Sasaki

✓ The feasibility of high-frequency transcranial electrical stimulation (TES) through screw electrodes placed in the skull was investigated for use in intraoperative monitoring of the motor pathways in patients who are in a state of general anesthesia during cerebral and spinal operations.

Motor evoked potentials (MEPs) were elicited by TES with a train of five square-wave pulses (duration 400 µsec, intensity ≤ 200 mA, frequency 500 Hz) delivered through metal screw electrodes placed in the outer table of the skull over the primary motor cortex in 42 patients. Myogenic MEPs to anodal stimulation were recorded from the abductor pollicis brevis (APB) and tibialis anterior (TA) muscles. The mean threshold stimulation intensity was 48 ± 17 mA for the APB muscles, and 112 ± 35 mA for the TA muscles. The electrodes were firmly fixed at the site and were not dislodged by surgical manipulation throughout the operation. No adverse reactions attributable to the TES were observed.

Passing current through the screw electrodes stimulates the motor cortex more effectively than conventional methods of TES. The method is safe and inexpensive, and it is convenient for intraoperative monitoring of motor pathways.

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Ryohei Otani, Akitake Mukasa, Masahiro Shin, Mayu Omata, Shunsaku Takayanagi, Shota Tanaka, Keisuke Ueki and Nobuhito Saito

OBJECTIVE

Chordoma is a slow-growing but clinically malignant tumor, and the prognosis remains poor in many cases. There is a strong impetus to develop more effective targeted molecular therapies. On this basis, the authors investigated the potential of Brachyury, a transcription factor involved in notochord development, as a candidate molecular target for the treatment of chordoma.

METHODS

Brachyury gene copy number and expression levels were evaluated by quantitative polymerase chain reaction in 27 chordoma samples, and the transcriptomes of Brachyury high-expression tumors (n = 4) and Brachyury low-expression tumors (n = 4) were analyzed. A chordoma cell line (U-CH2) was used to investigate the signaling pathways that regulate Brachyury expression.

RESULTS

All chordoma specimens expressed Brachyury, and expression levels varied widely. Patients with higher Brachyury expression had significantly shorter progression-free survival (5 months, n = 11) than those with lower expression (13 months, n = 16) (p = 0.03). Somatic copy number gain was confirmed in 12 of 27 (44%) cases, and copy number was positively correlated with Brachyury expression (R = 0.61, p < 0.001). Expression of PI3K/Akt pathway genes was upregulated in Brachyury high-expression tumors, and suppression of PI3K signaling led to reduced Brachyury expression and inhibition of cell growth in the U-CH2 chordoma cell line.

CONCLUSIONS

Activation of the PI3K/Akt pathway and Brachyury copy number gain are strongly associated with Brachyury overexpression, which appears to be a key event in chordoma growth regulation. These findings suggest that targeting Brachyury and PI3K/Akt signaling may be an effective new approach for treating chordoma.

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Hirotaka Hasegawa, Masahiro Shin, Kenji Kondo, Shunya Hanakita, Akitake Mukasa, Taichi Kin and Nobuhito Saito

OBJECTIVE

Skull base chondrosarcoma is one of the most intractable tumors because of its aggressive biological behavior and involvement of the internal carotid artery and cranial nerves (CNs). One of the most accepted treatment strategies for skull base chondrosarcoma has been surgical removal of the tumor in conjunction with proactive extensive radiation therapy (RT) to the original tumor bed. However, the optimal strategy has not been determined. The goal of this study was to evaluate the early results of endoscopic transnasal surgery (ETS).

METHODS

The authors retrospectively analyzed 19 consecutive patients who underwent ETS at their institution since 2010. Adjuvant stereotactic radiosurgery (SRS) was performed only for the small residual tumors that were not resected to avoid critical neurological complications. Histological confirmation and evaluation of the MIB-1 index was performed in all cases. The Kaplan-Meier method was used to determine the actuarial rate of tumor-free survival.

RESULTS

The median tumor volume and maximal diameter were 14.5 cm3 (range 1.4–88.4 cm3) and 3.8 cm (range 1.5–6.7 cm), respectively. Nine patients (47%) had intradural extension of the tumor. Gross-total resection was achieved in 15 (78.9%) of the 19 patients, without any disabling complications. In 4 patients, the surgery resulted in subtotal (n = 2, 11%) or partial (n = 2, 11%) resection because the tumors involved critical structures, including the basilar artery or the lower CNs. These 4 patients were additionally treated with SRS. The median follow-up duration was 47, 28, and 27 months after the diagnosis, ETS, and SRS, respectively. In 1 patient with an anterior skull base chondrosarcoma, the tumor relapsed in the optic canal 1 year later and was treated with a second ETS. Favorable tumor control was achieved in all other patients. The actuarial tumor control rate was 93% at 5 years. At the final follow-up, all patients were alive and able to perform independent activities of daily living without continuous neurological sequelae.

CONCLUSIONS

These preliminary results suggest that ETS can achieve sufficient radical tumor removal, resulting in comparative resection rates with fewer neurological complications to those in previous reports. Although the follow-up periods of these cases were relatively short, elective SRS to the small tumor remnant may be rational, achieving successful tumor control in some cases, instead of using proactive extensive RT. Thus, the addition of RT should be discussed with each patient, after due consideration of histological grading and biological behavior. To determine the efficacy of this strategy, a larger case series with a longer follow-up period is essential. However, this strategy may be able to establish evidence in the management of skull base chondrosarcoma, providing less-invasive and effective options as an initial step of treatment.

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Masahiro Shin, Kenji Kondo, Shunya Hanakita, Keigo Suzukawa, Taichi Kin, Masaaki Shojima, Daichi Nakagawa and Nobuhito Saito

OBJECT

In recent years, application of endoscopic transnasal surgery (ETS) has been expanded to orbital lesions, and preliminary results have started to be published for medially located soft mass lesions. However, reports on experience with endoscopic intraorbital surgery aimed at resection of invasive skull base tumors remains quite limited. This report presents the authors’ experience with ETS for locally aggressive tumors involving the orbit.

METHODS

ETS was performed for 15 cases of aggressive tumors involving the orbit: 5 meningiomas (meningothelial, n = 3; atypical, n = 1; anaplastic, n = 1), 4 chordomas, 2 chondrosarcomas, and 4 others (metastasis from systemic myxofibrosarcoma, schwannoma, inverted papilloma, and acinic cell carcinoma, n = 1 each). Among these, 9 tumors were located outside the periorbita and 6 inside the periorbita. In 6 intraperiosteal tumors, 5 were intraconal lesions, of which 3 arose in the muscle cone (anaplastic meningioma, optic sheath meningioma, and metastatic myxofibrosarcoma), and 2 meningothelial meningioma had invaded from the sphenoid ridge or the cavernous sinus into the muscle cone through the optic canal and the superior orbital fissure. A case of schwannoma originated around the cavernous sinus and pterygopalatine fossa and extended extraconally into the periorbita. Intraoperatively, ethmoid air cells and the lamina papyracea were removed, and extraperiosteal tumors were safely approached. For intraperiosteal tumors, the periorbita was widely opened, and the tumors were approached through the surgical window between the rectus and oblique muscles.

RESULTS

Gross-total resection was achieved for 12 of the 15 tumors, including 2 intraconal lesions. After surgery, exophthalmos resolved in all 8 patients with this symptom, and diplopia resolved in 5 of 6 patients. Improvement of visual symptoms was reported by 4 of 5 patients with loss of visual acuity or constriction of the visual field. Postoperatively, 1 patient showed mild, transient worsening of existing facial dysesthesia, and another showed transient ptosis and mild hypesthesia of the forehead on the affected side. All those symptoms resolved within 3 months. No patients showed enophthalmos, worsening of diplopia or visual function, or impairment of olfaction after surgery.

CONCLUSIONS

ETS appears acceptable as a less-invasive alternative for treating aggressive tumors involving the orbit. For extraperiosteal tumors, gross-total removal can generally be achieved without neurological complications. For intraperiosteal tumors, surgical indications should be carefully discussed, considering the relationship between the tumor and normal anatomy. Wide opening of the periorbital window is advocated to create a sufficient surgical pathway between the extraocular muscles, allowing a balance between functional preservation and successful tumor resection.