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Rong Hu, Jianjun Zhou, Chunxia Luo, Jiangkai Lin, Xianrong Wang, Xiaoguang Li, Xiuwu Bian, Yunqing Li, Qi Wan, Yanbing Yu and Hua Feng

Object

A glial scar is thought to be responsible for halting neuroregeneration following spinal cord injury (SCI). However, little quantitative evidence has been provided to show the relationship of a glial scar and axonal regrowth after injury.

Methods

In this study performed in rats and dogs, a traumatic SCI model was made using a weight-drop injury device, and tissue sections were stained with H & E for immunohistochemical analysis. The function and behavior of model animals were tested using electrophysiological recording and the Basso-Beattie-Bresnahan Locomotor Rating Scale, respectively. The cavity in the spinal cord after SCI in dogs was observed using MR imaging.

Results

The morphological results showed that the formation of an astroglial scar was defined at 4 weeks after SCI. While regenerative axons reached the vicinity of the lesion site, the glial scar blocked the extension of regrown axons. In agreement with these findings, the electrophysiological, behavioral, and in vivo MR imaging tests showed that functional recovery reached a plateau at 4 weeks after SCI. The thickness of the glial scars in the injured rat spinal cords was also measured. The mean thickness of the glial scar rostral and caudal to the lesion cavity was 107.00 ± 20.12 μm; laterally it was 69.92 ± 15.12 μm.

Conclusions

These results provide comprehensive evidence indicating that the formation of a glial scar inhibits axonal regeneration at 4 weeks after SCI. This study reveals a critical time window of postinjury recovery and a detailed spatial orientation of glial scar, which would provide an important basis for the development of therapeutic strategy for glial scar ablation.

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Hua-Jun Zhou, Hai-Nan Zhang, Tao Tang, Jian-Hua Zhong, Yong Qi, Jie-Kun Luo, Yuan Lin, Qi-Dong Yang and Xing-Qun Li

Object

Spontaneous intracerebral hemorrhage (ICH) is among the most intractable forms of stroke. Angiogenesis, an orchestrated balance between proangiogenic and antiangiogenic factors, is a fundamental process to brain development and repair by new blood vessel formation from preexisting ones and can be induced by ICH. Thrombospondin (TSP)–1 and TSP-2 are naturally occurring antiangiogenic factors. The aim of this study was to observe their expression in rat brains with ICH.

Methods

Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by stereotactic injection of collagenase VII or autologous blood into the right globus pallidus. The expression of TSP-1 and -2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription–polymerase chain reaction analysis.

Results

After the induction of ICH, some TSP1- or TSP2-immunoreactive microvessels resided around the hematoma for ~ 7 days and extended into a clot thereafter. Cerebral endothelial cells expressed the TSPs. The expression of TSP-1 and TSP-2 mRNA peaked at 4 and 14 days after collagenase-induced ICH, respectively.

Conclusions

Findings in this study suggest that ICH can alter the expression of TSP-1 and TSP-2, which may be involved in modulating angiogenesis in brains following ICH.

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Xiaohui Ren, Song Lin, Zhongcheng Wang, Lin Luo, Zhongli Jiang, Dali Sui, Zhiyong Bi, Yong Cui, Wenqing Jia, Yan Zhang, Lanbing Yu and Siyuan Chen

Object

Most intracranial epidermoid cysts typically present with long T1 and T2 signals on MR images. Other epidermoid cysts with atypical MR images are often misdiagnosed as other diseases. In this study the authors aimed to analyze the incidence and the clinical, radiological, and pathological features of atypical epidermoid cysts.

Methods

Among 428 cases of intracranial epidermoid cysts that were surgically treated between 2002 and 2008 at Beijing Tiantan Hospital, cases with an atypical MR imaging appearance were chosen for analysis. Clinical and pathological parameters were recorded and compared in patients with lesions demonstrating typical and atypical MR appearance.

Results

An atypical epidermoid cyst accounts for 5.6% of the whole series. Radiologically, 58.3% of atypical epidermoids were misdiagnosed as other diseases. Compared with a typical epidermoid cyst, atypical epidermoid lesions were significantly larger (p = 0.016, chi-square test). Pathologically, hemorrhage was found in 21 patients with atypical epidermoid cyst and is significantly correlated with granulation (p = 0.010, Fisher exact test). Old hemorrhage was found in 13 cases and was significantly correlated with cholesterol crystals. Twenty-one patients were followed up for 1.3–8.6 years after surgery. The 5- and 8-year survival rates were both 100%. Three patients experienced cyst recurrence. The 5- and 8-year recurrence-free rates were 95% and 81.4%, respectively.

Conclusions

Radiologically, an atypical epidermoid cyst should be differentiated from dermoid cyst, teratoma, schwannoma, glioma, craniopharyngioma, and cavernous angioma. A tendency toward spontaneous hemorrhage is confirmed in atypical epidermoid cysts, and a hypothesis was proposed for spontaneously intracystic hemorrhage in atypical epidermoid cysts. Follow-up confirmed long-term survival of patients with atypical epidermoid cysts.

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JianMing Luo, Bin Liu, ZeYu Xie, Shan Ding, ZeRui Zhuang, Lan Lin, YanChun Guo, Hui Chen and Xiaojun Yu

Object

The object of this study was to compare the effects and complications of manual and computer-aided shaping of titanium meshes for repairing large frontotemporoparietal skull defects following traumatic brain injury.

Methods

From March 2005 to June 2011, 161 patients with frontotemporoparietal skull defects were observed. Patients were divided into 2 groups according to the repair materials used for cranioplasty: 83 cases used computer-aided shaping for the titanium mesh, whereas the remaining 78 cases used a manually shaped titanium mesh. The advantages and disadvantages of the 2 methods were compared.

Results

No case of titanium mesh loosening occurred in either group. Subcutaneous fluid collection, titanium mesh tilt, and temporal muscle pain were the most common complications. In the manually shaped group, there were 14 cases of effusion, 10 cases of titanium mesh tilt, and 15 cases of temporal muscle pain. In the computer-aided group, there were 6 cases of effusion, 3 cases of titanium mesh tilt, and 6 cases of temporal muscle pain. The differences were significant between the 2 groups (p < 0.05). Other common complications were scalp infection, exposure of titanium mesh, epidural hematoma, and seizures. In the computer-aided group, the operative time decreased (p < 0.01), the number of screws used was reduced (p < 0.01), and the satisfaction of patients was significantly increased (p < 0.05).

Conclusions

Computer-aided shaping of titanium mesh for repairing large frontotemporoparietal skull defects decreases postoperative complications and the operative duration, reduces the number of screws used, increases the satisfaction of patients, and restores the appearance of the patient's head, making it an ideal choice for cranioplasty.

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Hua-Jun Zhou, Tao Tang, Han-Jin Cui, A-Li Yang, Jie-Kun Luo, Yuan Lin, Qi-Dong Yang and Xing-Qun Li

Object

Angiogenesis occurs after intracerebral hemorrhage (ICH). Thrombin mediates mitogenesis and survival in endothelial cells and induces angiogenesis. The present study aimed to clarify whether thrombin is involved in triggering ICH-related angiogenesis.

Methods

In the first part of the experiment, autologous blood (with or without hirudin) was injected to induce ICH. In the second part, rats received either 1 U (50 μl) thrombin or 50 μl 0.9% sterile saline. In both parts, 5-bromo-2-deoxyuridine (BrdU) was administered intraperitoneally. Brains were perfused to identify BrdU-positive/von Willebrand factor (vWF)–positive nuclei. The expression of hypoxia-inducible factor–1α (HIF-1α), vascular endothelial growth factor (VEGF), angiopoietin-1 (Ang-1) and Ang-2 was evaluated by immunohistochemistry and quantitative real-time reverse transcription polymerase chain reaction.

Results

After ICH, the number of BrdU-/vWF-positive nuclei increased until Day 14, and vessels positive for HIF-1α, VEGF, Ang-1, and Ang-2 were observed around the clot. Quantitative analysis showed that ICH upregulated expression of HIF-1α, VEGF, Ang-1, and Ang-2 notably compared with that in sham controls (p < 0.05). However, hirudin significantly inhibited these effects. After thrombin treatment, many BrdU-positive/vWF-positive nuclei and HIF-1α–, VEGF-, Ang-1– and Ang-2–positive vessels could be detected around the affected region.

Conclusions

Thrombin can induce angiogenesis in rat brains and may be an important trigger for ICH-related angiogenesis.

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Ali Liu, Jun-Mei Wang, Gui-Lin Li, Yi-Lin Sun, Shi-Bin Sun, Bin Luo and Mei-Hua Wang

Object

The goal of this study was to assess the clinical and pathological features of benign brain tumors that had been treated with Gamma Knife surgery (GKS) followed by resection.

Methods

In this retrospective chart review, the authors identified 61 patients with intracranial benign tumors who had undergone neurosurgical intervention after GKS. Of these 61 patients, 27 were male and 34 were female; mean age was 49.1 years (range 19–73 years). There were 24 meningiomas, 18 schwannomas, 14 pituitary adenomas, 3 hemangioblastomas, and 2 craniopharyngiomas. The interval between GKS and craniotomy was 2–168 months, with a median of 24 months; for 7 patients, the interval was 10 years or longer. For 21 patients, a craniotomy was performed before and after GKS; in 9 patients, pathological specimens were obtained before and after GKS. A total of 29 patients underwent GKS at the Beijing Tiantan Hospital. All specimens obtained by surgical intervention underwent histopathological examination.

Results

Most patients underwent craniotomy because of tumor recurrence and/or exacerbation of clinical signs and symptoms. Neuroimaging analyses indicated tumor growth in 42 patients, hydrocephalus in 10 patients with vestibular schwannoma, cystic formation with mass effect in 7 patients, and tumor hemorrhage in 13 patients, of whom 10 had pituitary adenoma. Pathological examination demonstrated that, regardless of the type of tumor, GKS mainly induced coagulative necrosis of tumor parenchyma and stroma with some apoptosis and, ultimately, scar formation. In addition, irradiation induced vasculature stenosis and occlusion and tumor degeneration as a result of reduced blood supply. GKS-induced vasculature reaction was rarely observed in patients with pituitary adenoma. Pathological analysis of tumor specimens obtained before and after GKS did not indicate increased tumor proliferation after GKS.

Conclusions

Radiosurgery is effective for intracranial benign tumors of small size and deep location and for tumor recurrence after surgical intervention; it is not effective for intracranial tumors with symptomatic mass effect. The radiobiological effects of stereotactic radiosurgery on the benign tumors are mainly caused by cellular and vascular mechanisms. Among the patients in this study, high-dose irradiation did not increase tumor proliferation. GKS can induce primary and secondary effects in tumors, which could last more than 10 years, thereby warranting long-term follow-up after GKS.

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Ren Lin, Lili Luo, Yiran Gong, Jingsheng Zheng, Shuiyue Wang, Junjie Du and Daoshu Luo

OBJECTIVE

The trigeminal root entry zone (TREZ) is a transitional zone between the central nervous system (CNS) and peripheral nervous system (PNS), adjacent to the brainstem. Microvascular compression of the TREZ has been considered to be the primary etiology in most cases of trigeminal neuralgia (TN), but whether epigenetic regulation is involved in the pathogenesis of TN is still unclear. Therefore, this study was designed to investigate the epigenetic regulation of histone H3 acetylation in the TREZ in an animal model of TN.

METHODS

An animal model of TN was established, and adult male Sprague-Dawley rats were randomly assigned to a TN group with trigeminal nerve root compression, sham operation group, TN+HDACi group (TN plus selective histone deacetylase inhibitor injection into the TREZ), or TN+Veh group (TN plus vehicle injection into the TREZ). To measure the length of the central portion of the TREZ from the junction of the trigeminal nerve root entering the pons to the interface of the dome-shaped CNS-PNS transitional zone, immunofluorescent staining of glia and glial nuclei was performed using glial fibrillary acidic protein (GFAP) antibody and DAPI, respectively. To investigate the acetylation of histone H3 within the TREZ in a TN animal model group and a sham operation group, localization of histone H3K9, H3K18, and H3K27 acetylation was examined via immunohistochemical staining methods.

RESULTS

Measurements of the CNS-PNS transitional zone in the TREZ revealed that the average length from the junction of the trigeminal nerve root connecting the pons to the glial fringe of the TREZ in the TN group was longer than that in the sham operation group (p < 0.05) and that the interface gradually migrated distally. Cells that stained positive for acetylated histone H3K9, H3K18, and H3K27 were distributed around both sides of the border of the CNS-PNS junction in the TREZ. The ratio of immunoreactive H3K9-, H3K18- and H3K27-positive cells in the TN group was obviously higher than that in the sham operation group on postoperative days 7, 14, 21, and 28 (p < 0.05).

CONCLUSIONS

These results suggested that chronic compression of the trigeminal nerve root may be involved in the pathogenesis of TN in an animal model by influencing the plasticity of the CNS-PNS transitional zone and the level of histone acetylation in the TREZ.

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Chia-An Wu, Huai-Che Yang, Yong-Sin Hu, Hsiu-Mei Wu, Chung-Jung Lin, Chao-Bao Luo, Wan-Yuo Guo, Cheng-Chia Lee, Kang-Du Liu and Wen-Yuh Chung

OBJECTIVE

Gamma Knife surgery (GKS) obliterates 65%–87% of cavernous sinus dural arteriovenous fistulas (CSDAVFs). However, the hemodynamic effect on GKS outcomes is relatively unknown. The authors thus used the classification scheme developed by Suh et al. to explore this effect.

METHODS

The authors retrospectively (1993–2016) included 123 patients with CSDAVFs who received GKS alone at the institute and classified them as proliferative type (PT; n = 23), restrictive type (RT; n = 61), or late restrictive type (LRT; n = 39) after analyzing their pre-GKS angiography images. Treatment parameters, the presence of numerous arterial feeders, and venous drainage numbers were compared across the CSDAVF types. Patients’ follow-up MR images were evaluated for the presence of complete obliteration. A Kaplan-Meier analysis was conducted to determine the correlation between CSDAVF types and outcomes.

RESULTS

The 36-month probability of complete obliteration was 74.3% for all patients, with no significant differences across types (p = 0.56). PT had the largest radiation volume (6.5 cm3, p < 0.001), the most isocenters (5, p = 0.015) and venous drainage routes (3, p < 0.001), and the lowest peripheral dose (16.6 Gy, p = 0.011) and isodose level coverage (64.3%, p = 0.006). CSDAVFs presenting with ocular patterns were less likely to be completely obliterated (hazard ratio 0.531, p = 0.009). After adjustment for age, CSDAVFs with more venous drainage routes were less likely to be completely obliterated (hazard ratio 0.784, p = 0.039).

CONCLUSIONS

GKS is an equally effective treatment option for all 3 CSDAVF types. Furthermore, the number of venous drainage routes may help in predicting treatment outcomes and making therapeutic decisions.

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Te Ming Lin, Huai Che Yang, Cheng Chia Lee, Hsiu Mei Wu, Yong Sin Hu, Chao Bao Luo, Wan Yuo Guo, Yi Hsuan Kao, Wen Yuh Chung and Chung Jung Lin

OBJECTIVE

Assessments of hemorrhage risk based on angioarchitecture have yielded inconsistent results, and quantitative hemodynamic studies have been limited to small numbers of patients. The authors examined whether cerebral hemodynamic analysis using quantitative digital subtraction angiography (QDSA) can outperform conventional DSA angioarchitecture analysis in evaluating the risk of hemorrhage associated with supratentorial arteriovenous malformations (AVMs).

METHODS

A cross-sectional study was performed by retrospectively reviewing adult supratentorial AVM patients who had undergone both DSA and MRI studies between 2011 and 2017. Angioarchitecture characteristics, DSA parameters, age, sex, and nidus volume were analyzed using univariate and multivariate logistic regression, and QDSA software analysis was performed on DSA images. Based on the QDSA analysis, a stasis index, defined as the inflow gradient divided by the absolute value of the outflow gradient, was determined. The receiver operating characteristic (ROC) curve was used to compare diagnostic performances of conventional DSA angioarchitecture analysis and analysis using hemodynamic parameters based on QDSA.

RESULTS

A total of 119 supratentorial AVM patients were included. After adjustment for age at diagnosis, sex, and nidus volume, the exclusive deep venous drainage (p < 0.01), observed through conventional angioarchitecture examination using DSA, and the stasis index of the most dominant drainage vein (p = 0.02), measured with QDSA hemodynamic analysis, were independent risk factors for hemorrhage. The areas under the ROC curves for the conventional DSA method (0.75) and QDSA hemodynamics analysis (0.73) were similar. A venous stasis index greater than 2.18 discriminated the hemorrhage group with a sensitivity of 52.6% and a specificity of 81.5%.

CONCLUSIONS

In QDSA, a higher stasis index of the most dominant drainage vein is an objective warning sign associated with supratentorial AVM rupture. Risk assessments of AVMs using QDSA and conventional DSA angioarchitecture were equivalent. Because QDSA is a complementary noninvasive approach without extra radiation or contrast media, comprehensive hemorrhagic risk assessment of cerebral AVMs should include both DSA angioarchitecture and QDSA analyses.

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Cheng-Chia Lee, Sanford P. C. Hsu, Chung-Jung Lin, Hsiu-Mei Wu, Yu-Wei Chen, Yung-Hung Luo, Chi-Lu Chiang, Yong-Sin Hu, Wen-Yuh Chung, Cheng-Ying Shiau, Wan-Yuo Guo, David Hung-Chi Pan and Huai-Che Yang

OBJECTIVE

The presence of epidermal growth factor receptor (EGFR) mutations in non–small cell lung cancer (NSCLC) has been associated with elevated radiosensitivity in vitro. However, results from clinical studies on radiosensitivity in cases of NSCLC with EGFR mutations are inconclusive. This paper presents a retrospective analysis of patients with NSCLC who underwent regular follow-up imaging after radiotherapy for brain metastases (BMs). The authors also investigated the influence of EGFR mutations on the efficacy of Gamma Knife radiosurgery (GKRS).

METHODS

This study included 264 patients (1069 BMs) who underwent GKRS treatment and for whom EGFR mutation status, demographics, performance status, and tumor characteristics were available. Radiological images were obtained at 3 months after GKRS and at 3-month intervals thereafter. Kaplan-Meier plots and Cox regression analysis were used to correlate EGFR mutation status and other clinical features with tumor control and overall survival.

RESULTS

The tumor control rates and overall 12-month survival rates were 87.8% and 65.5%, respectively. Tumor control rates in the EGFR mutant group versus the EGFR wild-type group were 90.5% versus 79.4% at 12 months and 75.0% versus 24.5% at 24 months. During the 2-year follow-up period after SRS, the intracranial response rate in the EGFR mutant group was approximately 3-fold higher than that in the wild-type group (p < 0.001). Cox regression multivariate analysis identified EGFR mutation status, extracranial metastasis, primary tumor control, and prescribed margin dose as predictors of tumor control (p = 0.004, p < 0.001, p = 0.004, and p = 0.026, respectively). Treatment with a combination of GKRS and tyrosine kinase inhibitors (TKIs) was the most important predictor of overall survival (p < 0.001).

CONCLUSIONS

The current study demonstrated that, among patients with NSCLC-BMs, EGFR mutations were independent prognostic factors of tumor control. It was also determined that a combination of GKRS and TKI had the most pronounced effect on prolonging survival after SRS. In select patient groups, treatment with SRS in conjunction with EGFR-TKIs provided effective tumor control for NSCLC-BMs.