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Qing-Song Lin, Wei-Xiong Wang, Yuan-Xiang Lin, Zhang-Ya Lin, Liang-Hong Yu, Yin Kang and De-Zhi Kang

OBJECTIVE

Glutamate excitotoxicity and neuronal apoptosis are suggested to contribute to early brain injury after subarachnoid hemorrhage (SAH). Annexin A7 (ANXA7) has been shown to regulate glutamate release. However, the role of ANXA7 in early brain injury after SAH has not been illustrated. In this study, we aimed to investigate the effect of ANXA7 knockdown in reducing the severity of early brain injury after SAH, and determine the underlying mechanisms.

METHODS

Endovascular perforation was performed to induce SAH in male Sprague-Dawley rats. ANXA7-siRNA was administered via intraventricular injection 5 days before SAH induction. Neurological test, evaluation of SAH grade, assessment of blood-brain barrier (BBB) permeability, measurement of brain water content, Western blot, double immunofluorescence staining, TUNEL staining, and enzyme-linked immunosorbent assay (ELISA) were performed at 24 hours of SAH induction.

RESULTS

ANXA7 protein expression increased significantly after SAH induction and was seen mainly in neurons. High expression of ANXA7 was associated with poor neurological status. ANXA7 knockdown dramatically ameliorated early brain injury through alleviating BBB disruption and brain edema. Further investigation of the mechanism showed that inhibiting ANXA7 expression can rescue neuronal apoptosis. In addition, ANXA7 knockdown also significantly reduced glutamate release, which was consistent with a significant increase of Bcl-2 expression and decreases of Bax and cleaved caspase-3 expression.

CONCLUSIONS

ANXA7 can induce neuronal apoptosis by affecting glutamate release in rats with SAH. Downregulating the expression of ANXA7 can significantly attenuate early brain injury after SAH. Future therapy targeting ANXA7 may be a promising new choice.

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Haihui Jiang, Zhe Zhang, Xiaohui Ren, Wei Zeng, Junmei Wang and Song Lin

OBJECTIVE

1p/19q co-deletion is a well-established tumor cell–specific chromosomal abnormality in oligodendroglial tumors. The endothelial cells (ECs) of oligodendroglial tumor vessels are considered to be normal cells that do not acquire mutations.

METHODS

A total of 30 samples from 16 male and 14 female patients (median age of 46.5 years) with a histological diagnosis of primary anaplastic oligodendroglioma (AO) were collected in the study. The immunofluorescence technique was used to identify vascular ECs, and the 1p/19q status was detected with fluorescence in situ hybridization. Kaplan-Meier plots were compared using the log-rank method.

RESULTS

The ECs in AO had a higher 1p36 (detected signal) deletion rate than 1q25 (reference signal) (p < 0.01) and a higher 19q13 (detected signal) deletion rate than 19p13 (reference signal) (p < 0.01). The survival analysis results showed that both the progression-free survival (PFS) and overall survival (OS) of the patients with 1p/19q–co-deleted ECs were significantly longer than those with 1p/19q-intact ECs (PFS, p < 0.001; OS, p < 0.001). This correlation was validated by an independent cohort. In addition, the Cox regression model revealed that 1p/19q co-deletion in ECs was an independent prognostic factor (HR 0.056 [95% CI 0.012–0.261], p < 0.001 for PFS; HR 0.061 [95% CI 0.013–0.280], p < 0.01 for OS).

CONCLUSIONS

1p/19q co-deletion and polysomy can be also found in the ECs of AO, which suggests that the ECs are, in part, tumor related and reflect a novel aspect of tumor angiogenesis.

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Yaxing Chen and Liangxue Zhou

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Jie Zhang, Dong-Xiao Zhuang, Cheng-Jun Yao, Ching-Po Lin, Tian-Liang Wang, Zhi-Yong Qin and Jin-Song Wu

OBJECT

The extent of resection is one of the most essential factors that influence the outcomes of glioma resection. However, conventional structural imaging has failed to accurately delineate glioma margins because of tumor cell infiltration. Three-dimensional proton MR spectroscopy (1H-MRS) can provide metabolic information and has been used in preoperative tumor differentiation, grading, and radiotherapy planning. Resection based on glioma metabolism information may provide for a more extensive resection and yield better outcomes for glioma patients. In this study, the authors attempt to integrate 3D 1H-MRS into neuronavigation and assess the feasibility and validity of metabolically based glioma resection.

METHODS

Choline (Cho)–N-acetylaspartate (NAA) index (CNI) maps were calculated and integrated into neuronavigation. The CNI thresholds were quantitatively analyzed and compared with structural MRI studies. Glioma resections were performed under 3D 1H-MRS guidance. Volumetric analyses were performed for metabolic and structural images from a low-grade glioma (LGG) group and high-grade glioma (HGG) group. Magnetic resonance imaging and neurological assessments were performed immediately after surgery and 1 year after tumor resection.

RESULTS

Fifteen eligible patients with primary cerebral gliomas were included in this study. Three-dimensional 1H-MRS maps were successfully coregistered with structural images and integrated into navigational system. Volumetric analyses showed that the differences between the metabolic volumes with different CNI thresholds were statistically significant (p < 0.05). For the LGG group, the differences between the structural and the metabolic volumes with CNI thresholds of 0.5 and 1.5 were statistically significant (p = 0.0005 and 0.0129, respectively). For the HGG group, the differences between the structural and metabolic volumes with CNI thresholds of 0.5 and 1.0 were statistically significant (p = 0.0027 and 0.0497, respectively). All patients showed no tumor progression at the 1-year follow-up.

CONCLUSIONS

This study integrated 3D MRS maps and intraoperative navigation for glioma margin delineation. Optimum CNI thresholds were applied for both LGGs and HGGs to achieve resection. The results indicated that 3D 1H-MRS can be integrated with structural imaging to provide better outcomes for glioma resection.

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Haihui Jiang, Yong Cui, Xiang Liu, Xiaohui Ren, Mingxiao Li and Song Lin

OBJECTIVE

The aim of this study was to investigate the relationship between extent of resection (EOR) and survival in terms of clinical, molecular, and radiological factors in high-grade astrocytoma (HGA).

METHODS

Clinical and radiological data from 585 cases of molecularly defined HGA were reviewed. In each case, the EOR was evaluated twice: once according to contrast-enhanced T1-weighted images (CE-T1WI) and once according to fluid attenuated inversion recovery (FLAIR) images. The ratio of the volume of the region of abnormality in CE-T1WI to that in FLAIR images (VFLAIR/VCE-T1WI) was calculated and a receiver operating characteristic curve was used to determine the optimal cutoff value for that ratio. Univariate and multivariate analyses were performed to identify the prognostic value of each factor.

RESULTS

Both the EOR evaluated from CE-T1WI and the EOR evaluated from FLAIR could divide the whole cohort into 4 subgroups with different survival outcomes (p < 0.001). Cases were stratified into 2 subtypes based on VFLAIR/VCE-T1WI with a cutoff of 10: a proliferation-dominant subtype and a diffusion-dominant subtype. Kaplan-Meier analysis showed a significant survival advantage for the proliferation-dominant subtype (p < 0.0001). The prognostic implication has been further confirmed in the Cox proportional hazards model (HR 1.105, 95% CI 1.078–1.134, p < 0.0001). The survival of patients with proliferation-dominant HGA was significantly prolonged in association with extensive resection of the FLAIR abnormality region beyond contrast-enhancing tumor (p = 0.03), while no survival benefit was observed in association with the extensive resection in the diffusion-dominant subtype (p = 0.86).

CONCLUSIONS

VFLAIR/VCE-T1WI is an important classifier that could divide the HGA into 2 subtypes with distinct invasive features. Patients with proliferation-dominant HGA can benefit from extensive resection of the FLAIR abnormality region, which provides the theoretical basis for a personalized resection strategy.

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Miaomiao Suo, Yahui Lin, Hui Yu, Weihua Song, Kai Sun, Yan Song, Yinhui Zhang, Channa Zhang, Yufang Zhu, Qi Pang, Rutai Hui and Jingzhou Chen

Object

Variants of Kallikreins have been shown to be risk factors for intracranial aneurysm (IA) in a Finnish population. In the present study, the authors investigated the correlation between polymorphisms in the Kallikrein gene cluster and IAs in the Chinese population.

Methods

The association of Kallikrein variants (rs1722561 and rs1701946) with sporadic IAs was tested in 308 cases and 443 controls. The differences in allelic frequencies between patients and the control group were evaluated with the chi-square test.

Results

The C allele of rs1722561 showed a significant reduction in the risk of sporadic IA (OR 0.71, 95% CI 0.53–0.95; p = 0.023). However, no association of the variant rs1701946 with sporadic IA was found (OR 0.78, 95% CI 0.57–1.06; p = 0.115).

Conclusions

The variant rs1722561 of Kallikreins might reduce the risk of sporadic IAs among individuals of Chinese Han ethnicity. This study confirms the association between Kallikreins and IAs.

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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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Xiao-hui Ren, Chun Chu, Chun Zeng, Yong-ji Tian, Zhen-yu Ma, Kai Tang, Lan-bing Yu, Xiang-li Cui, Zhong-cheng Wang and Song Lin

Object

Intracranial epidermoid cysts are rare, potentially curable, benign lesions that are sometimes associated with severe postoperative complications, including hemorrhage. Delayed hemorrhage, defined as one that occurred after an initial unremarkable postoperative CT scan, contributed to most cases of postoperative hemorrhage in patients with epidermoid cyst. In this study, the authors focus on delayed hemorrhage as one of the severe postoperative complications in epidermoid cyst, report its incidence and its clinical features, and analyze related clinical parameters.

Methods

There were 428 cases of intracranial epidermoid cysts that were surgically treated between 2002 and 2008 in Beijing Tiantan Hospital, and these were retrospectively reviewed. Among them, the cases with delayed postoperative hemorrhage were chosen for analysis. Clinical parameters were recorded, including the patient's age and sex, the chief surgeon's experience in neurosurgery, the year in which the operation was performed, tumor size, adhesion to neurovascular structures, and degree of resection. These parameters were compared in patients with and without delayed postoperative hemorrhage to identify risk factors associated with this entity.

Results

The incidences of postoperative hemorrhage and delayed postoperative hemorrhage in patients with epidermoid cyst were 5.61% (24 of 428) and 4.91% (21 of 428), respectively, both of which were significantly higher than that of postoperative hemorrhage in all concurrently treated intracranial tumors, which was 0.91% (122 of 13,479). The onset of delayed postoperative hemorrhage ranged from the 5th to 23rd day after the operation; the median time of onset was the 8th day. The onset manifestation included signs of intracranial hypertension and/or meningeal irritation (71.4%), brain herniation (14.3%), seizures (9.5%), and syncope (4.8%). Neuroimages revealed hematoma in 11 cases and subarachnoid hemorrhage in 10 cases. The rehemorrhage rate was 38.1% (8 of 21). The mortality rate for delayed postoperative hemorrhage was 28.6% (6 of 21). None of the clinical parameters was correlated with delayed postoperative hemorrhage (p > 0.05), despite a relatively lower p value for adhesion to neurovascular structures (p = 0.096).

Conclusions

Delayed postoperative hemorrhage contributed to most of the postoperative hemorrhages in patients with intracranial epidermoid cysts and was a unique postoperative complication with unfavorable outcomes. Adhesion to neurovascular structures was possibly related to delayed postoperative hemorrhage (p = 0.096).

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Jian-Cong Weng, Lai-Rong Song, Da Li, Liang Wang, Zhen Wu, Jun-Mei Wang, Gui-Lin Li, Wang Jia, Li-Wei Zhang and Jun-Ting Zhang

OBJECTIVE

Primary intracranial myxomas (PICMs) are extremely rare neoplasms, and their management and prognostic factors remain ambiguous. The authors aimed to elaborate the radiological features, evaluate the risk factors for progression-free survival (PFS), and propose a treatment protocol based on pooled data from cases treated at their institute and those found in the literature.

METHODS

Clinical data from all cases of PICMs treated at the authors’ institute and those cases reported in the English-language literature between 1987 and December 2017 were reviewed. The authors searched the Ovid MEDLINE, Embase, PubMed, and Cochrane databases using the keywords “myxoma” and “central nervous system,” “intracranial,” “cerebral,” “skull base,” “skull,” or “brain.” Previously published data were processed and used according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Risk factors in the pooled cohort were evaluated.

RESULTS

Cases from the authors’ institute included 21 males and 9 females, with a mean age of 35.7 ± 1.7 years. Gross-total resection (GTR) and non-GTR were achieved in 6 (20.0%) and 24 (80.0%) patients, respectively. After a mean follow-up of 86.7 ± 14.1 months, recurrence occurred in 6 (24%) patients, for a median PFS time of 85.2 months (range 36.0–136.0 months) and no deaths. In the literature between 1987 and 2017, 35 cases of PICM were identified in 14 males and 21 females with a mean age of 31.7 ± 3.2 years. GTR and non-GTR were achieved in 23 (65.7%) and 9 (25.7%) cases, respectively. After a mean follow-up of 25.8 ± 6.9 months (range 1.0–156.0 months), recurrence occurred in 4 (14.3%) patients, for a median PFS time of 11.0 months (range 3.0–36.0 months) and no deaths. Actuarial PFS rates at 1, 5, and 10 years were 93.0%, 80.6%, and 67.9%, respectively. A multivariate model demonstrated that GTR (HR 0.058, 95% CI 0.005–0.680, p = 0.023) was the only factor that favored PFS.

CONCLUSIONS

PICMs are rare neoplasms with a slightly higher occurrence in males. GTR was the only favorable factor for PFS. Based on statistical results, GTR alone, if tolerable, is advocated as the optimal treatment for PICM. Nevertheless, conservative excision may be preferred to avoid damage to vital structures. PICMs have a tendency to recur within a few years of the initial surgery if resection is incomplete; therefore, close postoperative follow-up is mandatory. Future studies with larger cohorts are necessary to verify the study findings.

Systematic review registration no.: CRD42018091517 (www.crd.york.ac.uk/prospero/)