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Sun-Chul Hwang, Soo-Bin Im, Bum-Tae Kim, and Won-Han Shin

Object

Twist-drill craniostomy (TDC) with closed-system drainage is an effective treatment option for chronic subdural hematoma (CSDH). Because the entry point for TDC has not been described in a definitive area, the aim of this study was to define the optimal twist-drill entry point for CSDH.

Methods

The authors selected 40 random cases involving selective catheter angiography of the external carotid artery, regardless of study purpose, to evaluate the course of the middle meningeal artery. Furthermore, 50 skull radiographs were reviewed to assess the relation of the vascular groove to the coronal suture. On the basis of the radiological anatomical study, the authors propose that the normal TDC entry point should be 1 cm anterior to the coronal suture at the level of the superior temporal line (STL). Thirty patients with symptomatic CSDH were treated using TDC with closed-system drainage at the proposed entry point. The thicknesses of the hematoma and the skull were measured at the proposed entry point. The congruence between the proposed entry point and postoperative craniostomy was estimated and complications were evaluated.

Results

In the radiological study, all the branches of the middle meningeal artery ran posterior to the coronal suture and the vascular grooves were also located posterior to the coronal suture at the level of the STL. The average distance of the vascular grooves was 8.0 ±5.8 mm. Thirty-five procedures were performed. The coronal suture and the STL could be identified clearly on brain CT scans. The mean thickness of the skull and the CSDH at the proposed point was 8 mm (range 5–13 mm) and 20 mm (range 10–28 mm), respectively. All the TDCs except 1 were congruent with the preoperative brain CT scans. One CSDH recurred 1 month after the first operation and was revised using the same procedure. No other complications occurred.

Conclusions

One centimeter anterior to the coronal suture at the level of the STL is suitable as the normal entry point of the TDC for symptomatic CSDH. The thickness of the CSDH can be measured at this point on a preoperative brain CT scan. Furthermore, the entry point on the scalp can be accurately estimated using surface landmarks.

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Kyeong-Sik Ryu, Chun-Kun Park, Sung-Chul Jun, and Han-Yong Huh

Object

The purposes of this retrospective study were to determine the radiological changes at the index and adjacent levels after cervical arthroplasty using the Bryan disc and Prodisc-C disc after a minimum 24 months follow-up, and to demonstrate the possible clinical factors related to these changes.

Methods

Following single-level cervical arthroplasty using either the Bryan disc or Prodisc-C, the degree of facet degeneration and other radiological changes at the index and adjacent levels were assessed by observing radiographs and CT scans at a minimum 24 months after the operations. These findings were determined in relation to the clinical outcome, various perioperative factors, and prosthesis factors. Thirty-six patients were included in this investigation (19 in the Bryan disc group and 17 in the Prodisc-C group).

Results

At the index level, progression of facet arthrosis (PFA) was observed in 7 of 36 levels (1 level with the Bryan disc, 6 with the Prodisc-C). At adjacent levels, PFA was minimally observed. Heterotopic ossification (HO) was observed at 19 levels (11 with the Bryan disc, 8 with Prodisc-C). Progression of facet arthrosis at the index segments was positively related to malposition of the prosthesis on the frontal plane, and decreased postoperative functional spinal unit range of motion at the index level. Occurrence of HO was correlated with the preoperative calcification of the posterior longitudinal ligament at the operated level, regardless of prosthesis type. Clinical outcome and the occurrence of PFA or HO did not show any significant relationship.

Conclusions

This study demonstrates that the incidence of PFA at the index level is 19.4% after a minimum 24-month follow-up, and occurs more frequently in the Prodisc-C group. Progression of facet arthrosis is related to less functional spinal unit range of motion and anterior placement of the prosthesis. The occurrence rate of HO is high, regardless of the type of prosthesis, and it is significantly correlated with preoperative calcification of the posterior longitudinal ligament at the operated level.

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Jung Ho Han, Dong Gyu Kim, Hyun-Tai Chung, Chul-Kee Park, Sun Ha Paek, Jeong Eun Kim, Hee-Won Jung, and Dae Hee Han

Object

In this paper the authors analyzed the clinical and neuroimaging outcomes of patients with cerebral arteriovenous malformations (AVMs) after Gamma Knife surgery (GKS), focusing on the analysis of the radiation injury rate depending on the AVM volume.

Methods

Between 1997 and 2004, 277 consecutive patients with cerebral AVMs were treated with GKS. Of these patients, 218 were followed up for ≥ 2 years. The mean age was 31 ± 15 years, the median AVM volume was 3.4 cm3 (range 0.17–35.2 cm3), the median marginal dose was 18.0 Gy (range 10.0–25.0 Gy), and the mean follow-up duration was 44 ± 20 months. The authors reduced the prescription dose by various amounts, depending on the AVM volume and location as prescribed in the classic guideline to avoid irreversible radiation injuries.

Results

The angiographic obliteration rate was 66.4% overall, and it was 81.7, 53.1, and 12.5% for small, medium, and large AVMs, respectively. The overall annual bleeding rate was 1.9%. The annual bleeding rate was 0.44 and 4.64% for small and large AVMs, respectively. Approximately 20% of the patients showed severe postradiosurgery imaging (PRI) changes. The rate of PRI change was 11.4, 33.3, and 9.5% for small, medium, and large AVM volume groups, respectively, and a permanent radiation injury developed in 5.1% of patients.

Conclusions

By using the reduced dose from what is usually prescribed, the authors were able to obtain outcomes in small AVMs that were comparable to the outcomes described in previous reports. However, medium AVMs appear to still be at risk for adverse radiation effects. Last, in large AVMs, the authors were able to attain a tolerable rate of radiation injury; however, the clinical outcomes were quite disappointing following administration of a reduced dose of GKS for large AVMs.

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Chul Han, Michael J. Lang, Candice L. Nguyen, Ernesto Luna Melendez, Shwetal Mehta, Gregory H. Turner, Michael T. Lawton, and S. Paul Oh

OBJECTIVE

Hereditary hemorrhagic telangiectasia is the only condition associated with multiple inherited brain arteriovenous malformations (AVMs). Therefore, a mouse model was developed with a genetics-based approach that conditionally deleted the causative activin receptor-like kinase 1 (Acvrl1 or Alk1) gene. Radiographic and histopathological findings were correlated, and AVM stability and hemorrhagic behavior over time were examined.

METHODS

Alk1-floxed mice were crossed with deleter mice to generate offspring in which both copies of the Alk1 gene were deleted by Tagln-Cre to form brain AVMs in the mice. AVMs were characterized using MRI, MRA, and DSA. Brain AVMs were characterized histopathologically with latex dye perfusion, immunofluorescence, and Prussian blue staining.

RESULTS

Brains of 55 Tagln-Cre+;Alk1f/f mutant mice were categorized into three groups: no detectable vascular lesions (group 1; 23 of 55, 42%), arteriovenous fistulas (AVFs) with no nidus (group 2; 10 of 55, 18%), and nidal AVMs (group 3; 22 of 55, 40%). Microhemorrhage was observed on MRI or MRA in 11 AVMs (50%). AVMs had the angiographic hallmarks of early nidus opacification, a tangle of arteries and dilated draining veins, and rapid shunting of blood flow. Latex dye perfusion confirmed arteriovenous shunting in all AVMs and AVFs. Microhemorrhages were detected adjacent to AVFs and AVMs, visualized by iron deposition, Prussian blue staining, and macrophage infiltration using CD68 immunostaining. Brain AVMs were stable on serial MRI and MRA in group 3 mice (mean age at initial imaging 2.9 months; mean age at last imaging 9.5 months).

CONCLUSIONS

Approximately 40% of transgenic mice satisfied the requirements of a stable experimental AVM model by replicating nidal anatomy, arteriovenous hemodynamics, and microhemorrhagic behavior. Transgenic mice with AVFs had a recognizable phenotype of hereditary hemorrhagic telangiectasia but were less suitable for experimental modeling. AVM pathogenesis can be understood as the combination of conditional Alk1 gene deletion during embryogenesis and angiogenesis that is hyperactive in developing and newborn mice, which translates to a congenital origin in most patients but an acquired condition in patients with a confluence of genetic and angiogenic events later in life. This study offers a novel experimental brain AVM model for future studies of AVM pathophysiology, growth, rupture, and therapeutic regression.

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Yun-Sik Dho, Yong Hwy Kim, Young-Bem Se, Doo Hee Han, Jung Hee Kim, Chul-Kee Park, Kyu-Chang Wang, and Dong Gyu Kim

OBJECTIVE

The endoscopic endonasal approach (EEA) is commonly used for the treatment of craniopharyngioma; therefore, it is essential to analyze outcomes in order to understand the benefits and drawbacks. The goal of this paper was to evaluate the clinical features and outcomes associated with this treatment approach.

METHODS

From July 2010 to March 2016, 82 adult craniopharyngioma patients underwent an EEA at the authors’ institution. Of these cases, intraoperative records and immediate postoperative MR images were available for 68 patients. The patients underwent systemized endocrinological evaluation. Eighteen of 68 patients who underwent EEA for recurrence or regrowth of residual lesions after previous surgical management were excluded in the analysis of the anatomical tumor classification. The authors retrospectively analyzed preoperative clinical features and previous anatomical classifications, focusing on the relationship of the pituitary stalk and tumor, to determine predictive factors for the clinical outcome, such as the extent of resection, visual function, endocrinological function, recurrence rate, and complications.

RESULTS

The mean tumor size was 2.5 cm (3.1 cm for primary tumors and 1.9 cm for recurrent lesions). Gross-total resection (GTR) was achieved in 62 (91.1%) patients (48 [96.0%] patients with primary tumors and 14 [77.8%] patients with recurrent tumors). The rate of GTR was higher in the primary group than in the group with recurrence (p = 0.038). The overall pre- and postoperative visual impairment scale (VIS) scores were 40.8 and 22.1, respectively (50.9 and 14.3 in the primary group and 30.7 and 29.9 in patients with recurrence, respectively). The improvement rate in VIS score was higher in the primary group than in the recurrent group (p = 0.001). Endocrinological function was improved in 4 patients (5.9%) and deteriorated in 32 of 68 patients (47.1%). Tumor invasion into the center of the pituitary stalk affected the postoperative outcomes most significantly. Cognitive dysfunction was observed in 22 patients before surgery and improved in 20 patients (90.9%) after surgery. Hydrocephalus was found in 7 patients and resolved after surgery in all cases. CSF leakage occurred in 2 (2.9%) of 68 patients and was repaired by revision surgery in both patients. Ten patients without CSF leakage also received antibiotics for the treatment of meningitis. The infection rate was higher in the recurrent group. Postoperative endocrinological evaluation showed no deficits in 12 patients and panhypopituitarism in 55 patients. The remaining patient had growth hormone deficiency. Forty-three patients had new-onset diabetes insipidus, and 1 patient had persistent diabetes insipidus after surgery. There were 2 (2.9%) cases of recurrence during the mean 30.7-month follow-up period; one patient underwent radiosurgery and the other underwent reoperation.

CONCLUSIONS

The EEA resulted in excellent surgical outcomes and acceptable morbidity rates, regardless of the anatomical location of the tumor. Invasion of the craniopharyngioma into the center of the pituitary stalk has strong predictive power for postoperative endocrinological outcome.

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Ji Hoon Phi, Seung-Ki Kim, Joongyub Lee, Chul-Kee Park, Il Han Kim, Hyo Seop Ahn, Hee Young Shin, In-One Kim, Hee-Won Jung, Dong Gyu Kim, Sun Ha Paek, and Kyu-Chang Wang

Object

Intracranial germ cell tumors (GCTs) frequently present with bifocal lesions in both the suprasellar and pineal areas. The pathogenesis of these bifocal GCTs has been the subject of controversy. Bifocal GCTs may be caused by synchronous tumors or by metastatic spread of tumor cells from one site to the other. The prognosis associated with bifocal GCTs has also been a cause of concern.

Methods

The authors constructed a single-institution patient cohort comprising 181 patients with intracranial GCTs. The clinical characteristics of bifocal GCTs were compared with those of suprasellar and pineal GCTs.

Results

Bifocal GCTs were observed in 23 patients (12.8%). Eighteen patients presented with bifocal GCTs that were diagnosed as germinomas, but 5 patients exhibited mixed GCTs. Analyses of age distributions and comparisons of tumor sizes were compatible with a model of a metastatic origin of bifocal GCTs. Eleven patients (47.8%) presenting with bifocal GCTs exhibited tumor seeding at presentation. Tumor seeding was significantly associated with bifocal lesions (p < 0.001). Patients with bifocal germinomas showed significantly shorter event-free survival and overall survival than did those presenting with germinomas from a single site of origin.

Conclusions

Bifocal GCTs are not restricted to germinomas, as had been previously reported, but do include mixed GCTs. The authors hypothesize that bifocal GCTs may result from the metastatic spread of suprasellar or pineal GCTs. The bifocal presentation of germinomas may be a poor prognostic sign and should alert clinicians to the possibility of a disseminated disease.

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Yong Hwy Kim, Chiman Jeon, Young-Bem Se, Sang Duk Hong, Ho Jun Seol, Jung-II Lee, Chul-Kee Park, Dong Gyu Kim, Hee-Won Jung, Doo Hee Han, Do-Hyun Nam, and Doo-Sik Kong

OBJECTIVE

The endoscopic endonasal approach for treating primary skull base malignancies involving the clivus is a formidable task. The authors hypothesized that tumor involvement of nearby critical anatomical structures creates hurdles to endoscopic gross-total resection (GTR). The aim of this study was to retrospectively review the clinical outcomes of patients who underwent an endoscopic endonasal approach to treat primary malignancies involving the clivus and to analyze prognostic factors for GTR.

METHODS

Between January 2009 and November 2015, 42 patients underwent the endoscopic endonasal approach for resection of primary skull base malignancies involving the clivus at 2 independent institutions. Clinical data; tumor locations within the clivus; and anatomical involvement of the cavernous or paraclival internal carotid artery, cisternal trigeminal nerve, hypoglossal canal, and dura mater were investigated to assess the extent of resection. Possible prognostic factors affecting GTR were also analyzed.

RESULTS

Of the 42 patients, 37 were diagnosed with chordomas and 5 were diagnosed with chondrosarcomas. The mean (± SD) preoperative tumor volume was 25.2 ± 30.5 cm3 (range 0.8–166.7 cm3). GTR was achieved in 28 patients (66.7%) and subtotal resection in 14 patients (33.3%). All tumors were classified as upper (n = 17), middle (n = 17), or lower (n = 8) clival tumors based on clival involvement, and as central (24 [57.1%]) or paramedian (18 [42.9%]) based on laterality of the tumor. Univariate analysis identified the tumor laterality (OR 6.25, 95% CI 1.51–25.86; p = 0.011) as significantly predictive of GTR. In addition, the laterality of the tumor was found to be a statistically significant predictor in multivariate analysis (OR 41.16, 95% CI 1.12–1512.65; p = 0.043).

CONCLUSIONS

An endoscopic endonasal approach can provide favorable clinical and surgical outcomes. However, the tumor laterality should be considered as a potential obstacle to total removal.

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Kyung-Ho Park, Jaeho Lee, Chul-Gyu Yoo, Young Whan Kim, Sung Koo Han, Young-Soo Shim, Seung-Ki Kim, Kyu-Chang Wang, Byung-Kyu Cho, and Choon-Taek Lee

Object. Malignant glioma could be an ideal candidate for local gene therapy because its invasion is local and it has little metastatic potential. A low expression level and high degradation activity of p27 are known to constitute an independent poor prognostic factor in patients with malignant glioma. In this study, the authors investigated the roles of wild-type p27 and mutant p27 on the treatment of malignant glioma.

Methods. The authors used two adenoviruses: one expressed wild-type p27 (ad-p27wt) and the other, containing a mutation at the major metabolic site, expressed mutant p27 (ad-p27mt). The antitumor effects of the two adenoviruses were compared with respect to cell growth arrest, cell cycle alteration, apoptosis induction, and in vitro tumorigenicity in three glioblastoma mutiforme (GBM) cell lines and in a primary GBM cell line. Transduction with ad-p27wt or ad-p27mt induced the production of p27 and the dephosphorylation of pRB. The protein level of mutant p27 was significantly higher than that of wild-type p27. The ad-p27wt induced cell cycle arrest at the G1—S transition point, whereas the ad-p27mt induced arrest at the G2—M point. Both ad-p27wt and ad-p27mt induced a growth-inhibiting effect, apoptosis, and suppression of in vitro tumorigenicity; however, ad-p27mt displayed a stronger antitumor effect than ad-p27wt in brain tumor cell lines.

Conclusions. Gene therapy involving p27, especially mutant p27, has the potential to become a novel and powerful therapy for malignant glioma.

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Roh-Eul Yoo, Tae Jin Yun, Young Dae Cho, Jung Hyo Rhim, Koung Mi Kang, Seung Hong Choi, Ji-hoon Kim, Jeong Eun Kim, Hyun-Seung Kang, Chul-Ho Sohn, Sun-Won Park, and Moon Hee Han

OBJECTIVE

Arterial spin labeling perfusion-weighted imaging (ASL-PWI) enables quantification of tissue perfusion without contrast media administration. The aim of this study was to explore whether cerebral blood flow (CBF) from ASL-PWI can reliably predict angiographic vascularity of meningiomas.

METHODS

Twenty-seven patients with intracranial meningiomas, who had undergone preoperative ASL-PWI and digital subtraction angiography prior to resection, were included. Angiographic vascularity was assessed using a 4-point grading scale and meningiomas were classified into 2 groups: low vascularity (Grades 0 and 1; n = 11) and high vascularity (Grades 2 and 3; n = 16). Absolute CBF, measured at the largest section of the tumor, was normalized to the contralateral gray matter. Correlation between the mean normalized CBF (nCBF) and angiographic vascularity was determined and the mean nCBF values of the 2 groups were compared. Diagnostic performance of the nCBF for differentiating between the 2 groups was assessed.

RESULTS

The nCBF had a significant positive correlation with angiographic vascularity (ρ = 0.718; p < 0.001). The high-vascularity group had a significantly higher nCBF than the low-vascularity group (3.334 ± 2.768 and 0.909 ± 0.468, respectively; p = 0.003). At the optimal nCBF cutoff value of 1.733, sensitivity and specificity for the differential diagnosis of the 2 groups were 69% (95% CI 41%–89%) and 100% (95% CI 72%–100%), respectively. The area under the receiver operating characteristic curve was 0.875 (p < 0.001).

CONCLUSIONS

ASL-PWI may provide a reliable and noninvasive means of predicting angiographic vascularity of meningiomas. It may thus assist in selecting potential candidates for preoperative digital subtraction angiography and embolization in clinical practice.