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Ying Chen, Linyan Zhang, Tingting Qin, Zhenzhen Wang, Ying Li and Bing Gu

OBJECTIVE

Various implanted materials are used in neurosurgery; however, there remains a lack of pooled data on infection rates (IRs) and infective bacteria over past decades. The goal of this study was to investigate implant infections in neurosurgical procedures in a longitudinal retrospective study and to evaluate the IRs of neurosurgically implanted materials and the distribution of pathogenic microorganisms.

METHODS

A systematic literature search was conducted using PubMed and Web of Science databases for the time period between 1968 and 2018. Neurosurgical implant infections were studied in 5 subgroups, including operations or diseases, implanted materials, bacteria, distribution by country, and time periods, which were obtained from the literature and statistically analyzed. In this meta-analysis, statistical heterogeneity across studies was tested by using p values and I2 values between studies of associated pathogens. Egger’s test was used for assessing symmetries of funnel plots with Stata 11.0 software. Methodological quality was assessed to judge the risk of bias according to the Cochrane Handbook.

RESULTS

A total of 22,971 patients from 227 articles satisfied the study’s eligibility criteria. Of these, 1118 cases of infection were reported, and the overall IR was 4.87%. In this study, the neurosurgical procedures or disorders with the top 3 IRs included craniotomy (IR 6.58%), cranioplasty (IR 5.89%), and motor movement disorders (IR 5.43%). Among 13 implanted materials, the implants with the top 3 IRs included polypropylene-polyester, titanium, and polyetheretherketone (PEEK), which were 8.11%, 8.15%, and 7.31%, respectively. Furthermore, the main causative pathogen was Staphylococcus aureus and the countries with the top 3 IRs were Denmark (IR 11.90%), Korea (IR 10.98%), and Mexico (IR 9.26%). Except for the low IR from 1998 to 2007, the overall implant IR after neurosurgical procedures was on the rise.

CONCLUSIONS

In this study, the main pathogen in neurosurgery was S. aureus, which can provide a certain reference for the clinic. In addition, the IRs of polypropylene-polyester, titanium, and PEEK were higher than other materials, which means that more attention should be paid to them. In short, the total IR was high in neurosurgical implants and should be taken seriously.

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Xu Bang-Zong, Pan Hong-Xue, Li Ke-Ming, Chen Xi-Jin, Tian Ying-Dei, Li Yong-Lin and Liu Jian

✓ A biomembrane was developed from pig peritoneum treated with 0.65% glutaraldehyde. This was evaluated for use as a dural substitute in an animal model and in a patient population. After being treated with the glutaraldehyde solution, the biomembrane lost its antigenicity while its collagen underwent an irreversible cross-linking reaction, causing it to become a stable nonviable polymer resistant to absorption by the host. The biomembrane was used experimentally in 43 procedures on 20 dogs and was applied clinically in 614 patients. The results demonstrated that it is an acceptable material for the repair of dural defects, with the following advantages: 1) it is nontoxic to the body and brain tissues, with minimal tissue reaction; 2) its biophysical properties facilitate watertight closure with sutures; 3) its distensibility makes it suitable for decompressive surgical dural repair; and 4) its visceral surface is extremely smooth, causing virtually no adhesions with the brain tissue while the outer surface readily heals with the subcutaneous tissue.

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Xiang Zou, Liangfu Zhou, Wei Zhu, Ying Mao and Liang Chen

OBJECT

Intracranial dural arteriovenous fistulas (DAVFs) are complex intracranial vascular malformations that can lead to hemorrhage. The authors recently found that chronic local hypoperfusion seems to be the main cause of angiogenesis in the dura mater, which leads to the formation of DAVFs. As a natural derivative of estradiol, 2-methoxyestradiol (2-ME) has an antiangiogenic effect and can be used safely in patients with advanced carcinoid tumors. This study was conducted to examine the antiangiogenic effects of 2-ME on a rat DAVF model.

METHODS

Male Sprague-Dawley rats (n = 72) were used in the experiments. Intracranial venous hypertension was induced for modeling, and 2-ME was used in the early or late stage for treatment. The effects were examined by immunohistochemistry, Western blot analysis, and quantitative real-time polymerase chain reaction assays.

RESULTS

2-Methoxyestradiol significantly reduced angiogenesis in the dura in early- and late-intervention treatment groups, as proven by the results of immunohistochemical staining, Western blotting, real-time polymerase chain reaction assays, and microvessel density counts. The antiangiogenic effect even lasted for up to 2 weeks after 2-ME cessation.

CONCLUSIONS

These data collectively suggest that 2-ME can reduce the angiogenic effect caused by venous hypertension in a rat DAVF model, mainly by suppressing the inhibitor of differentiation 1 (ID-1) and hypoxia-inducible factor 1α (HIF-1α) pathways.

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Ying-Chao Lin, Chao-Cheng Huang and Han-Jung Chen

✓ Lipomatous tumors can contain uncommon or rare components (such as fibrolipoma or angiolipoma) that may result in the development of symptoms. To the best of the authors' knowledge, lipoma associated with an osseous component has not been previously reported. A case of intraspinal extradural tumor composed of both adipose and bone tissue is presented. Current theories on the cause of lipoma with an osseous component are discussed. The tumor was histologically confirmed to be an osteolipoma, and the patient recovered well after resection.

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Chia-Hua Chen, Pin-Yuan Chen, You-Yu Lin, Li-Ying Feng, Shin-Han Chen, Chia-Yuan Chen, Yin-Cheng Huang, Chiung-Yin Huang, Shih-Ming Jung, Leslie Y. Chen and Kuo-Chen Wei

OBJECTIVE

Despite intensive medical treatment, patients with glioblastoma (grade IV glioma [GBM]) have a low 5-year survival rate of 5.5%. In this study, the authors tried to improve currently used therapies by identification of a therapeutic target, IGFBP3, for glioma treatment.

METHODS

IGFBP3 RNA expression in 135 patients newly diagnosed with glioma was correlated with clinicopathological factors. Immunohistochemical analysis was performed to determine IGFBP3 protein expression in glioma specimens. The effect of IGFBP3 depletion on cell proliferation was examined using IGFBP3 knockdown glioma cells. Intracranial infusion of IGFBP3 siRNAs was performed to evaluate the effect of IGFBP3 depletion in mouse intracranial xenograft models.

RESULTS

We demonstrated higher IGFBP3 expression in GBM than in tumor margin and grade II glioma. IGFBP3 expression was not only positively correlated with tumor grades but also associated with tumor histology and IDH1/2 mutation status. Additionally, higher IGFBP3 expression predicted shorter overall survival in glioma and GBM proneural subgroup patients. In vitro cell culture studies suggested IGFBP3 knockdown suppressed cell proliferation and induced cell cycle G2/M arrest as well as apoptosis in glioma cells. Also, accumulation of DNA double-strand breaks and γH2AX was observed in IGFBP3 knockdown cells. IGFBP3 knockdown delayed in vivo tumor growth in mouse subcutaneous xenograft models. Furthermore, convection-enhanced delivery of IGFBP3 siRNA to mouse brain suppressed intracranial tumor growth and prolonged survival of tumor-bearing mice.

CONCLUSIONS

Our findings suggest IGFBP3 predicts poor outcome of glioma patients and is a potential therapeutic target for which depletion of its expression suppresses tumor growth through inducing apoptosis and accumulation of DNA damage in glioma cells.

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Xiang Zou, Zehan Wu, Wei Zhu, Liang Chen, Ying Mao and Fan Zhao

OBJECTIVE

Intracerebral hemorrhage (ICH) is a fatal disease with high morbidity and mortality, which may be followed by white matter injury (WMI) due to the local oxidizing reaction induced by iron (Fe). In this study, the authors examined the effect of the tetracycline antibiotic minocycline on Fe-induced WMI and c-Jun N-terminal kinase (JNK) activation in rats.

METHODS

Thirty-six male Sprague-Dawley rats underwent an intracaudate injection of saline, Fe, or Fe + minocycline. Another 36 rats had an intracaudate injection of autologous blood and were treated with minocycline or vehicle (saline). Biomarkers of both WMI and JNK activation were examined.

RESULTS

In the Fe-injection group, minocycline suppressed WMI labeled by β-amyloid precursor protein (β-APP) and degraded myelin basic protein (dMBP)/MBP ratio. Protein levels of phosphorylated-JNK were increased after Fe injection, and could be suppressed by minocycline treatment. In the autologous blood–injection group, β-APP and dMBP/MBP levels increased in the ipsilateral site compared with the contralateral site, which could be suppressed by 7 days of minocycline intervention.

CONCLUSIONS

Iron plays a critical role in WMI after ICH, which can be suppressed by minocycline through reducing the damage induced by Fe.

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Tao-Chen Lee, Kang Lu, Lin-Cheng Yang, Hsuan-Ying Huang and Cheng-Loong Liang

Object. Because modern imaging techniques now allow for early diagnosis of spinal tuberculosis, more conservative management options are possible. The authors evaluated the effectiveness of transpedicular instrumentation for treatment of thoracolumbar and lumbar spinal tuberculosis in patients with mild bone destruction and the main symptom of “instability catch” (a sudden painful “snap” that occurs when one extends from a forward bent to an upright position).

Methods. Eighteen patients (nine men and nine women, age range 49–71 years) with spinal tuberculosis were treated with transpedicular instrumentation that was supplemented with posterolateral fusion and chemotherapy. All patients were wheelchair dependent or bed-ridden due to severe instability catch, with a mean symptom duration of 2.5 months (range 1–6 months). Two contiguous vertebrae were involved in 17 patients, and a single vertebrae was involved in one. In five patients mild neurological deficits (Frankel Grade D) were present. During surgery, the screws were implanted into the two nonaffected pedicles nearest the lesion to stabilize the involved segments. No attempt at radical debridement or neural decompression was undertaken. The follow-up period ranged from 21 to 40 months. Postoperatively the instability catch was relieved within 10 days (excellent outcome) and within 1 month (good outcome) in seven and eight patients, respectively, and within 3 months (fair outcome) in two; in the remaining patient, the symptom did not resolve (poor outcome). A short duration of symptoms (generally < 3 months) and bone destruction of less than 50% in the involved vertebral bodies were observed in patients who made a good or excellent outcome. During the follow-up period, good maintenance of spinal alignment, stabilization of the involved segment, and resolution of the inflammatory process were shown; however, there was no strong evidence that fusion had occurred at the bony defect. Patients in whom a fair outcome was achieved experienced a longer duration of symptoms, and in each, one vertebral body with greater than 50% bone destruction was demonstrated. However, good maintenance of spinal alignment was also shown during the follow-up period. The patient whose outcome was poor had the longest history (6 months) of symptoms and the most extensive involvement of the spine (> 50% destruction of two adjacent lumbar vertebral bodies). Postoperatively, implant failure occurred and the patient developed a wound infection.

Conclusions. Transpedicular instrumentation provides rapid relief of instability catch and prevents late angular deformity in patients with thoracolumbar and lumbar spinal tuberculosis in whom limited (< 50%) bone destruction of the involved vertebral bodies has been shown and whose main symptom is instability catch.

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Wei-Ying Yue, Su-Huan Yu, Shi-Guang Zhao and Zhong-Ping Chen

Object

Astrocytoma may progress rapidly or remain stable for many years. To clarify whether molecular characteristics could be prognostic factors, several cell cycling–associated molecular alterations in the diffuse astrocytoma have been investigated.

Methods

Thirty-three patients in whom WHO Grade II astrocytoma had been initially diagnosed were assigned to 1 of 3 groups. Group 1 consisted of 10 patients with malignant progression; the tumor had recurred within 5 years and histological analysis had confirmed that the tumor progressed to Grade III or IV. Group 2 consisted of 10 patients in whom there was no malignant progression; the tumor recurred within 5 years, but histological analysis confirmed that the tumor remained at Grade II. Group 3 consisted of 13 patients who did not experience recurrence within 5 years. Expression of Ki 67, TP53, p27, and p21 was examined using immunohistochemical analysis for the tumor samples obtained during the first and second (in recurrent cases) surgeries. Exons 5, 7, and 8 of TP53 were scanned by DNA sequencing.

Results

The Ki 67 labeling index expression was significantly higher in Group 1 (even though it was similar between initial and recurrent tumors) than that of Group 3 (p < 0.05). However, there was no difference between Group 2 (both initial and recurrent tumors) and Group 3. The TP53 protein accumulation was also higher in Group 1 than in Group 2 or 3 (p < 0.05); a difference in TP53 expression was not found between Groups 2 and 3. The p27 and p21 was expressed in all cases, but no predictive values were found. The p53 mutation was found only in 6 cases in Group 1.

Conclusions

Overexpression of TP53, TP53 mutation, and Ki 67 labeling index could be molecular markers in astrocytomas predicting malignant progression.

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Sheng-Tzung Tsai, Wei-Yi Chuang, Chung-Chih Kuo, Paul C. P. Chao, Tsung-Ying Chen, Hsiang-Yi Hung and Shin-Yuan Chen

OBJECT

Deep brain stimulation (DBS) surgery under general anesthesia is an alternative option for patients with Parkinson’s disease (PD). However, few studies are available that report whether neuronal firing can be accurately recorded during this condition. In this study the authors attempted to characterize the neuronal activity of the subthalamic nucleus (STN) and elucidate the influence of general anesthetics on neurons during DBS surgery in patients with PD. The benefit of median nerve stimulation (MNS) for localization of the dorsolateral subterritory of the STN, which is involved in sensorimotor function, was explored.

METHODS

Eight patients with PD were anesthetized with desflurane and underwent contralateral MNS at the wrist during microelectrode recording of the STN. The authors analyzed the spiking patterns and power spectral density (PSD) of the background activity along each penetration track and determined the spatial correlation to the target location, estimated mated using standard neurophysiological procedures.

RESULTS

The dorsolateral STN spiking pattern showed a more prominent bursting pattern without MNS and more oscillation with MNS. In terms of the neural oscillation of the background activity, beta-band oscillation dominated within the sensorimotor STN and showed significantly more PSD during MNS (p < 0.05).

CONCLUSIONS

Neuronal firing within the STN could be accurately identified and differentiated when patients with PD received general anesthetics. Median nerve stimulation can enhance the neural activity in beta-band oscillations, which can be used as an index to ensure optimal electrode placement via successfully tracked dorsolateral STN topography.

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E-Jian Lee, Ming-Yang Lee, Guan-Liang Chang, Li-Hsuan Chen, Yu-Ling Hu, Tsung-Ying Chen and Tian-Shung Wu

Object. The authors examined whether delayed treatment with Mg++ would reduce brain infarction and improve electrophysiological and neurobehavioral recovery following cerebral ischemia—reperfusion.

Methods. Male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion for 90 minutes followed by 72 hours of reperfusion. Magnesium sulfate (750 µmol/kg) or vehicle was given via intracarotid infusion at the beginning of reperfusion. Neurobehavioral outcome and somatosensory evoked potentials (SSEPs) were examined before and 72 hours after ischemia—reperfusion. Brain infarction was assessed after the rats had died.

Before ischemia—reperfusion, stable SSEP waveforms were recorded after individual fore- and hindpaw stimulations. At 72 hours of perfusion the SSEPs recorded from ischemic fore- and hindpaw cortical fields were depressed in vehicle-injected animals and the amplitudes decreased to 19 and 27% of baseline, respectively (p < 0.001). Relative to controls, the amplitudes of SSEPs recorded from both ischemic fore- and hindpaw cortical field in the Mg++-treated animals were significantly improved by 23% (p < 0.005) and 39% (p < 0.001) of baselines, respectively. In addition, Mg++ improved sensory and motor neurobehavioral outcomes by 34% (p < 0.01) and 24% (p < 0.05), respectively, and reduced cortical (p < 0.05) and striatal (p < 0.05) infarct sizes by 42 and 36%, respectively.

Conclusions. Administration of Mg++ at the commencement of reperfusion enhances electrophysiological and neurobehavioral recovery and reduces brain infarction after cerebral ischemia—reperfusion. Because Mg++ has already been used clinically, it may be worthwhile to investigate it further to see if it holds potential benefits for patients with ischemic stroke and for those who will undergo carotid endarterectomy.