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Shunya Hanakita, Tomoyuki Koga, Hiroshi Igaki, Naoya Murakami, Soichi Oya, Masahiro Shin and Nobuhito Saito

Object

Atypical meningioma often recurs even after resection. As a salvage modality, radiotherapy or stereotactic radiosurgery (SRS) is attempted for this aggressive tumor. This retrospective study was performed to evaluate the efficacy of SRS that involved Gamma Knife surgery (GKS) for atypical meningioma.

Methods

The authors reviewed records from 22 patients with histologically proven atypical meningioma who underwent GKS for 28 lesions at the authors' institute. The median patient age was 70 years (range 24–91 years), and the median tumor volume for each procedure was 6.0 cm3 (range 1.6–38.7 cm3). The margin dose ranged from 14 to 20 Gy (median 18 Gy). Follow-up periods ranged from 3 months to 98 months (median 23.5 months).

Results

In total, 39 GKS procedures were performed for 28 lesions. The local control rates at 1, 2, and 5 years were 74%, 39%, and 16%, respectively. Volume less than 6 cm3 (p = 0.01), a margin dose higher than 18 Gy (p = 0.02), and a Karnofsky Performance Scale (KPS) score of 90 or more (p = 0.02) were factors associated with a longer duration of tumor control in the univariate analysis.

Conclusions

Atypical meningioma could be more successfully controlled when a higher margin dose was used to treat patients with a good performance (KPS score of ≥ 90) status and smaller tumor volumes. It would be desired if patients are treated with a relatively higher margin dose, ideally as high as the dose applied for malignant tumor. A boost SRS after fractionated radiotherapy may be effective to achieve better local control.

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Hirokazu Takami, Masahiro Shin, Masafumi Kuroiwa, Ayako Isoo, Kan Takahashi and Nobuhito Saito

Cystic malformations in the posterior cranial fossa result from developmental failure in the paleocerebellum and meninges. The authors present the case of an infant with hydrocephalus associated with cystic dilation of the foramina of Magendie and Luschka.

This 7-month-old female infant presented with sudden onset of tonic-clonic seizures. Computed tomography revealed tetraventricular hydrocephalus. Magnetic resonance imaging demonstrated a cyst communicating with the fourth ventricle and projecting to the cisterna magna and the cerebellopontine cisterns through the foramina of Magendie and Luschka. A suboccipital craniotomy was performed for removal of the cyst wall, and the transparent membrane covering the foramen of Magendie was removed under a microscope. After the surgery, the patient's hydrocephalus improved and a phase contrast cine MR imaging study showed evidence of normal CSF flow at the level of the third and fourth ventricles. Three weeks later, however, the hydrocephalus recurred. An endoscopic third ventriculocisternostomy was performed to address the possibility of stagnant CSF flow in the posterior cranial fossa, but the hydrocephalus continued. Finally the patient underwent placement of a ventriculoperitoneal shunt, resulting in improvement of her symptoms and resolution of the hydrocephalus.

On the basis of this experience and previously published reports, the authors speculate that the cystic malformation in their patient could be classified in a continuum of persistent Blake pouch cysts. Hydrocephalus was caused by a combination of obstruction of CSF flow at the outlets of the fourth ventricle and disequilibrium between CSF production and absorption capacity.

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Keisuke Takai, Taichi Kin, Hiroshi Oyama, Masaaki Shojima and Nobuhito Saito

Object

There have been significant advances in understanding the angioarchitecture of spinal dural arteriovenous fistulas (AVFs). However, the major intradural retrograde venous drainage system has not been investigated in detail, including the most proximal sites of intradural radiculomedullary veins as they connect to the dura mater, which are the final targets of interruption in both microsurgical and endovascular treatments.

Methods

Between April 1984 and March 2011, 27 patients with 28 AVFs were treated for spinal dural AVFs at the authors' university hospital. The authors assessed vertebral levels of feeding arteries and dural AVFs by using conventional digital subtraction angiography. They also assessed 3D locations of the most proximal sites of intradural radiculomedullary veins and the 3D positional relationship between the major intradural retrograde venous drainage system and intradural neural structures, including the spinal cord, spinal nerves, and the artery of Adamkiewicz, by using operative video recordings plus 3D rotational angiography and/or 3D computer graphics. In addition, they statistically assessed the clinical results of 27 cases. Of these lesions, 23 were treated with open microsurgery and the rest were treated with endovascular methods.

Results

Feeding arteries consisted of T2–10 intercostal arteries with 19 lesions, T-12 subcostal arteries with 3 lesions, and L1–3 lumbar arteries with 6 lesions. The 3D locations of the targets of interruption (the most proximal sites of intradural radiculomedullary veins as they connect to the dura mater) were identified at the dorsolateral portion of the dura mater adjacent to dorsal roots in all 19 thoracic lesions, whereas they were identified at the ventrolateral portion of the dura mater adjacent to ventral roots in 7 (78%) of 9 cases of conus medullaris/lumbar lesions (p < 0.001). The major intradural retrograde venous drainage system was located dorsal to the spinal cord in all 19 thoracic lesions, whereas it was located ventral to the spinal cord in 4 (44%) of 9 cases of conus/lumbar lesions (p = 0.006). In 3 (11%) of 27 cases, AVFs had a common origin of the artery of Adamkiewicz. In 2 lumbar lesions, the artery of Adamkiewicz ascended very close to the vein because of its ventral location. Although all lesions were successfully obliterated without major complications and both gait and micturition status significantly improved (p = 0.005 and p = 0.015, respectively), conus/lumbar lesions needed careful differential diagnosis from ventral intradural perimedullary AVFs, because the ventral location of these lesions contradicted the Spetzler classification system.

Conclusions

The angioarchitecture of spinal dural AVFs in the thoracic region is strikingly different from that in conus/lumbar regions with regard to the intradural retrograde venous drainage system. One should keep in mind that spinal dural AVFs are not always dorsal types, especially in conus/lumbar regions.

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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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Katsushige Watanabe, Nobuhito Saito, Makoto Taniguchi, Takaaki Kirino and Tomio Sasaki

Object. The frequency, nature, and history of subjective taste disturbance before and after vestibular schwannoma (VS) surgery was investigated.

Methods. Personal interviews were conducted in 108 patients with unilateral VS. Abnormalities in taste perception, either a significant reduction or a change in character, were experienced by 31 patients (28.7%) before surgery and by 37 (34.3%) after tumor removal. Preoperative taste disturbance worsened after surgery in five (16.1%) of the 31 patients, remained unchanged in eight (25.8%), improved in two (6.5%), and became normal in 16 (51.6%). Taste disturbance occurred postoperatively in 22 (28.6%) of 77 patients who had experienced no preoperative taste disturbance. The mean onset of the abnormality after resection was 1.1 ± 1.7 months. Postoperative taste disturbance resolved in 24 of the 37 patients (64.9%) within 1 year after onset.

Conclusions. Subjective taste disturbance was common before and after VS removal, and the natural history of this condition was very variable in the pre- and postoperative periods. All patients who undergo surgery for VS should receive appropriate counseling about the likelihood and course of postoperative complications, including dysfunction of the sensory component of the facial nerve.

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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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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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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.

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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.