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Yi-gang Huang, Liang Chen, Yu-dong Gu and Guang-rong Yu

Object

In Erb palsy, the C-7 spinal nerve has been found to be more subject to avulsion than the C-5 and C-6 spinal nerves. This study investigated the morphological and biomechanical characteristics of the semiconic posterosuperior ligaments (SPLs) at the C-5, C-6, and C-7 spinal nerves in neonates.

Methods

Twenty-four brachial plexuses from 12 fresh neonate cadavers were used in this study. In 12 brachial plexuses from 6 cadavers, the following studies were performed with respect to the SPLs at the C-5, C-6, and C-7 spinal nerves: gross observation of morphological and histological characteristics; measurement of length, thickness, and width; and a semiquantitative analysis of collagen. In the other 6 cadavers, biomechanical tension testing was performed bilaterally on the C5–7 SPLs to assess the tensile strength of the ligaments.

Results

The C5–7 spinal nerves are fixed to the transverse process through the SPL, a structure not observed at the C-8 and T-1 spinal nerves. Except for the width of the SPL insertion on the spinal nerve, which was found to increase gradually from C-5 to C-7, there was no statistically significant difference in the dimensions of the C-5, C-6, and C-7 SPLs. The sectional area percentage of collagen was 51% ± 10% in SPLs for C-5, 51% ± 11% for C-6, and 41% ± 10% for C-7; and this percentage was significantly lower in SPLs for C-7 than for C-5 or C-6 (1-way ANOVA, F = 4.3, p = 0.02; Tukey honestly significant difference test, p = 0.04 and 0.04, respectively). Sharpey fibers were observed at the transverse process origin of the SPL at C-5 and C-6 but not at C-7. Biomechanical tension testing showed that the mean failure load was 6.6 ± 0.9 N for the C-5 SPL, 6.4 ± 1.0 N for the C-6 SPL, and 5.4 ± 0.9 N for the C-7 SPL, and the failure load was significantly lower in SPLs at C-7 than in those at C-5 or C-6 (1-way ANOVA, F = 5.1, p = 0.01; Tukey honestly significant difference, p = 0.01 and 0.048, respectively). Nine of 12 C-7 SPLs failed at their origin from the transverse process, while only 4 of 12 C-5 SPLs and 3 of 12 C-6 SPLs failed at the origin site.

Conclusions

These findings suggest that the lower density of collagen and absence of Sharpey fibers decrease the biomechanical properties of the C-7 SPL, and this may account for the higher frequency of avulsion of the C-7 spinal nerve (in comparison with the C-5 or C-6 nerve) in Erb palsy.

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Zhi Chen, Jingyu Chen, Hongpin Miao, Fei Li, Hua Feng and Gang Zhu

Hemorrhagic events associated with cerebral paragonimiasis are not rare, especially in children and adolescents; however, angiographic evidence of cerebrovascular involvement has not been reported. The authors describe angiographic abnormalities of the cerebral arteries seen in 2 children in whom cerebral paragonimiasis was associated with hemorrhagic stroke. The patients presented with acute intracerebral and subarachnoid hemorrhage. Angiography revealed a beaded appearance and long segmental narrowing of arteries, consistent with arteritis. In both patients, involved vessels were seen in the area of the hemorrhage. The vascular changes and the hemorrhage, together with new lesions that developed close to the hemorrhage and improved after praziquantel treatment, were attributed to paragonimiasis. Further study of the frequency and mechanism of hemorrhagic cerebrovascular complications associated with cerebral paragonimiasis is needed.

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Yizhi Liu, Jiaoxue Qiu, Zhong Wang, Wanchun You, Lingyun Wu, Chengyuan Ji and Gang Chen

OBJECT

Oxidative stress and the inflammatory response are thought to promote brain damage in the setting of subarachnoid hemorrhage (SAH). Previous reports have shown that dimethylfumarate (DMF) can activate the Kelch-like ECH-associated protein 1–nuclear factor erythroid 2-related factor 2–antioxidant-responsive element (Keap1-Nrf2-ARE) system in vivo and in vitro, which leads to the downregulation of oxidative stress and inflammation. The aim of this study was to evaluate the potential neuroprotective effect of DMF on SAH-induced brain injury in rats.

METHODS

Rats were subjected to SAH by the injection of 300 μl of autologous blood into the chiasmatic cistern. Rats in a DMF-treated group were given 15 mg/kg DMF twice daily by oral gavage for 2 days after the onset of SAH. Cortical apoptosis, neural necrosis, brain edema, blood-brain barrier impairment, learning deficits, and changes in the Keap1-Nrf2-ARE pathway were assessed.

RESULTS

Administration of DMF significantly ameliorated the early brain injury and learning deficits induced by SAH in this animal model. Treatment with DMF markedly upregulated the expressions of agents related to Keap1-Nrf2-ARE signaling after SAH. The inflammatory response and oxidative stress were downregulated by DMF therapy.

CONCLUSIONS

DMF administration resulted in abatement of the development of early brain injury and cognitive dysfunction in this prechiasmatic cistern SAH model. This result was probably mediated by the effect of DMF on the Keap1-Nrf2-ARE system.

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Wen-Han Hu, Chao Zhang, Kai Zhang, Fan-Gang Meng, Ning Chen and Jian-Guo Zhang

Object

Whether selective amygdalohippocampectomy (SelAH) has similar seizure outcomes and better neuropsychological outcomes compared with anterior temporal lobectomy (ATL) is a matter of debate. The aim of this study was to compare the 2 types of surgery with respect to seizure outcomes and changes in IQ scores.

Methods

PubMed, Embase, and the Cochrane Library were searched for relevant studies published between January 1990 and September 2012. Studies comparing SelAH and ATL with respect to seizure and intelligence outcomes were included. Two reviewers assessed the quality of the included studies and independently extracted the data. Odds ratios and standardized mean deviations with 95% confidence intervals were used to compare pooled proportions of freedom from seizures and changes in IQ scores between the SelAH and ATL groups.

Results

Three prospective and 10 retrospective studies were identified involving 745 and 766 patients who underwent SelAH and ATL, respectively. The meta-analysis demonstrated a statistically significant reduction in the odds of seizure freedom for patients who underwent SelAH compared with those who underwent ATL (OR 0.65 [95% CI 0.51–0.82], p = 0.0005). The differences between the changes in all IQ scores after the 2 types of surgery were not statistically significant, regardless of the side of resection.

Conclusions

Selective amygdalohippocampectomy statistically reduced the odds of being seizure free compared with ATL, but the clinical significance of this reduction needs to be further validated by well-designed randomized trials. Selective amygdalohippocampectomy did not have better outcomes than ATL with respect to intelligence.

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Liang Li, Jiantao Yang, Bengang Qin, Honggang Wang, Yi Yang, Jintao Fang, Gang Chen, Xiaolin Liu, Zhehui Tu and Liqiang Gu

OBJECTIVE

Human acellular nerve allograft applications have increased in clinical practice, but no studies have quantified their influence on reconstruction outcomes for high-level, greater, and mixed nerves, especially the brachial plexus. The authors investigated the functional outcomes of human acellular nerve allograft reconstruction for nerve gaps in patients with brachial plexus injury (BPI) undergoing contralateral C7 (CC7) nerve root transfer to innervate the upper trunk, and they determined the independent predictors of recovery in shoulder abduction and elbow flexion.

METHODS

Forty-five patients with partial or total BPI were eligible for this retrospective study after CC7 nerve root transfer to the upper trunk using human acellular nerve allografts. Deltoid and biceps muscle strength, degree of shoulder abduction and elbow flexion, Semmes-Weinstein monofilament test, and static two-point discrimination (S2PD) were examined according to the modified British Medical Research Council (mBMRC) scoring system, and disabilities of the arm, shoulder, and hand (DASH) were scored to establish the function of the affected upper limb. Meaningful recovery was defined as grades of M3–M5 or S3–S4 based on the scoring system. Subgroup analysis and univariate and multivariate logistic regression analyses were conducted to identify predictors of human acellular nerve allograft reconstruction.

RESULTS

The mean follow-up duration and the mean human acellular nerve allograft length were 48.1 ± 10.1 months and 30.9 ± 5.9 mm, respectively. Deltoid and biceps muscle strength was grade M4 or M3 in 71.1% and 60.0% of patients. Patients in the following groups achieved a higher rate of meaningful recovery in deltoid and biceps strength, as well as lower DASH scores (p < 0.01): age < 20 years and age 20–29 years; allograft lengths ≤ 30 mm; and patients in whom the interval between injury and surgery was < 90 days. The meaningful sensory recovery rate was approximately 70% in the Semmes-Weinstein monofilament test and S2PD. According to univariate and multivariate logistic regression analyses, age, interval between injury and surgery, and allograft length significantly influenced functional outcomes.

CONCLUSIONS

Human acellular nerve allografts offered safe reconstruction for 20- to 50-mm nerve gaps in procedures for CC7 nerve root transfer to repair the upper trunk after BPI. The group in which allograft lengths were ≤ 30 mm achieved better functional outcome than others, and the recommended length of allograft in this procedure was less than 30 mm. Age, interval between injury and surgery, and allograft length were independent predictors of functional outcomes after human acellular nerve allograft reconstruction.

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Qiang Tan, Qianwei Chen, Yin Niu, Zhou Feng, Lin Li, Yihao Tao, Jun Tang, Liming Yang, Jing Guo, Hua Feng, Gang Zhu and Zhi Chen

OBJECTIVE

Intracerebral hemorrhage (ICH) is associated with a high rate of mortality and severe disability, while fibrinolysis for ICH evacuation is a possible treatment. However, reported adverse effects can counteract the benefits of fibrinolysis and limit the use of tissue-type plasminogen activator (tPA). Identifying appropriate fibrinolytics is still needed. Therefore, the authors here compared the use of urokinase-type plasminogen activator (uPA), an alternate thrombolytic, with that of tPA in a preclinical study.

METHODS

Intracerebral hemorrhage was induced in adult male Sprague-Dawley rats by injecting autologous blood into the caudate, followed by intraclot fibrinolysis without drainage. Rats were randomized to receive uPA, tPA, or saline within the clot. Hematoma and perihematomal edema, brain water content, Evans blue fluorescence and neurological scores, matrix metalloproteinases (MMPs), MMP mRNA, blood-brain barrier (BBB) tight junction proteins, and nuclear factor–κB (NF-κB) activation were measured to evaluate the effects of these 2 drugs in ICH.

RESULTS

In comparison with tPA, uPA better ameliorated brain edema and promoted an improved outcome after ICH. In addition, uPA therapy more effectively upregulated BBB tight junction protein expression, which was partly attributed to the different effects of uPA and tPA on the regulation of MMPs and its related mRNA expression following ICH.

CONCLUSIONS

This study provided evidence supporting the use of uPA for fibrinolytic therapy after ICH. Large animal experiments and clinical trials are required to further explore the efficacy and safety of uPA in ICH fibrinolysis.

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Zhaoxia Zou, Yufang Yin, Jenny Lin, Li-chen J. Hsu, Vanessa L. Brandon, Fan Yang, Richard Jove, Rahul Jandial, Gang Li and Mike Y. Chen

OBJECT

Despite recent advances, metastatic melanoma remains a terminal disease, in which life-threatening brain metastasis occurs in approximately half of patients. Sorafenib is a multikinase inhibitor that induces apoptosis of melanoma cells in vitro. However, systemic administration has been ineffective because adequate tissue concentrations cannot be achieved. This study investigated if convection-enhanced delivery (CED) of sorafenib would enhance tumor control and survival via inhibition of the signal transducer and activator of transcription 3 (Stat3) pathway in a murine model of metastatic brain melanoma.

METHODS

Melanoma cells treated with sorafenib in vitro were examined for signaling and survival changes. The effect of sorafenib given by CED was assessed by bioluminescent imaging and animal survival.

RESULTS

The results showed that sorafenib induced cell death in the 4 established melanoma cell lines and in 1 primary cultured melanoma cell line. Sorafenib inhibited Stat3 phosphorylation in HTB65, WYC1, and B16 cells. Accordingly, sorafenib treatment also decreased expression of Mcl-1 mRNA in melanoma cell lines. Because sorafenib targets multiple pathways, the present study demonstrated the contribution of the Stat3 pathway by showing that mouse embryonic fibroblast (MEF) Stat3 +/+ cells were significantly more sensitive to sorafenib than MEF Stat3 −/− cells. In the murine model of melanoma brain metastasis used in this study, CED of sorafenib increased survival by 150% in the treatment group compared with animals receiving the vehicle control (p < 0.01). CED of sorafenib also significantly abrogated tumor growth.

CONCLUSIONS

The data from this study indicate that local delivery of sorafenib effectively controls brain melanoma. These findings validate further investigation of the use of CED to distribute molecularly targeted agents.

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Guo-chen Sun, Xiao-lei Chen, Yuan-zheng Hou, Xin-guang Yu, Xiao-dong Ma, Gang Liu, Lei Liu, Jia-shu Zhang, Hao Tang, Ru-Yuan Zhu, Ding-Biao Zhou and Bai-nan Xu

OBJECTIVE

Endoscopic removal of intracerebral hematomas is becoming increasingly common, but there is no standard technique. The authors explored the use of a simple image-guided endoscopic method for removal of spontaneous supratentorial hematomas.

METHODS

Virtual reality technology based on a hospital picture archiving and communications systems (PACS) was used in 3D hematoma visualization and surgical planning. Augmented reality based on an Android smartphone app, Sina neurosurgical assist, allowed a projection of the hematoma to be seen on the patient's scalp to facilitate selection of the best trajectory to the center of the hematoma. A obturator and transparent sheath were used to establish a working channel, and an endoscope and a metal suction apparatus were used to remove the hematoma.

RESULTS

A total of 25 patients were included in the study, including 18 with putamen hemorrhages and 7 with lobar cerebral hemorrhages. Virtual reality combined with augmented reality helped in achieving the desired position with the obturator and sheath. The median time from the initial surgical incision to completion of closure was 50 minutes (range 40–70 minutes). The actual endoscopic operating time was 30 (range 15–50) minutes. The median blood loss was 80 (range 40–150) ml. No patient experienced postoperative rebleeding. The average hematoma evacuation rate was 97%. The mean (± SD) preoperative Glasgow Coma Scale (GCS) score was 6.7 ± 3.2; 1 week after hematoma evacuation the mean GCS score had improved to 11.9 ± 3.1 (p < 0.01).

CONCLUSIONS

Virtual reality using hospital PACS and augmented reality with a smartphone app helped precisely localize hematomas and plan the appropriate endoscopic approach. A transparent sheath helped establish a surgical channel, and an endoscope enabled observation of the hematoma's location to achieve satisfactory hematoma removal.

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Robert M. Starke, David J. McCarthy, Ching-Jen Chen, Hideyuki Kano, Brendan McShane, John Lee, David Mathieu, Lucas T. Vasas, Anthony M. Kaufmann, Wei Gang Wang, Inga S. Grills, Mohana Rao Patibandla, Christopher P. Cifarelli, Gabriella Paisan, John A. Vargo, Tomas Chytka, Ladislava Janouskova, Caleb E. Feliciano, Rafael Rodriguez-Mercado, Daniel A. Tonetti, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

In this multicenter study, the authors reviewed the results obtained in patients who underwent Gamma Knife radiosurgery (GKRS) for dural arteriovenous fistulas (dAVFs) and determined predictors of outcome.

METHODS

Data from a cohort of 114 patients who underwent GKRS for cerebral dAVFs were compiled from the International Gamma Knife Research Foundation. Favorable outcome was defined as dAVF obliteration and no posttreatment hemorrhage or permanent symptomatic radiation-induced complications. Patient and dAVF characteristics were assessed to determine predictors of outcome in a multivariate logistic regression analysis; dAVF-free obliteration was calculated in a competing-risk survival analysis; and Youden indices were used to determine optimal radiosurgical dose.

RESULTS

A mean margin dose of 21.8 Gy was delivered. The mean follow-up duration was 4 years (range 0.5–18 years). The overall obliteration rate was 68.4%. The postradiosurgery actuarial rates of obliteration at 3, 5, 7, and 10 years were 41.3%, 61.1%, 70.1%, and 82.0%, respectively. Post-GRKS hemorrhage occurred in 4 patients (annual risk of 0.9%). Radiation-induced imaging changes occurred in 10.4% of patients; 5.2% were symptomatic, and 3.5% had permanent deficits. Favorable outcome was achieved in 63.2% of patients. Patients with middle fossa and tentorial dAVFs (OR 2.4, p = 0.048) and those receiving a margin dose greater than 23 Gy (OR 2.6, p = 0.030) were less likely to achieve a favorable outcome. Commonly used grading scales (e.g., Borden and Cognard) were not predictive of outcome. Female sex (OR 1.7, p = 0.03), absent venous ectasia (OR 3.4, p < 0.001), and cavernous carotid location (OR 2.1, p = 0.019) were predictors of GKRS-induced dAVF obliteration.

CONCLUSIONS

GKRS for cerebral dAVFs achieved obliteration and avoided permanent complications in the majority of patients. Those with cavernous carotid location and no venous ectasia were more likely to have fistula obliteration following radiosurgery. Commonly used grading scales were not reliable predictors of outcome following radiosurgery.

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Robert M. Starke, David J. McCarthy, Ching-Jen Chen, Hideyuki Kano, Brendan J. McShane, John Lee, Mohana Rao Patibandla, David Mathieu, Lucas T. Vasas, Anthony M. Kaufmann, Wei Gang Wang, Inga S. Grills, Christopher P. Cifarelli, Gabriella Paisan, John Vargo, Tomas Chytka, Ladislava Janouskova, Caleb E. Feliciano, Nanthiya Sujijantarat, Charles Matouk, Veronica Chiang, Judith Hess, Rafael Rodriguez-Mercado, Daniel A. Tonetti, L. Dade Lunsford and Jason P. Sheehan

OBJECTIVE

The authors performed a study to evaluate the hemorrhagic rates of cerebral dural arteriovenous fistulas (dAVFs) and the risk factors of hemorrhage following Gamma Knife radiosurgery (GKRS).

METHODS

Data from a cohort of patients undergoing GKRS for cerebral dAVFs were compiled from the International Radiosurgery Research Foundation. The annual posttreatment hemorrhage rate was calculated as the number of hemorrhages divided by the patient-years at risk. Risk factors for dAVF hemorrhage prior to GKRS and during the latency period after radiosurgery were evaluated in a multivariate analysis.

RESULTS

A total of 147 patients with dAVFs were treated with GKRS. Thirty-six patients (24.5%) presented with hemorrhage. dAVFs that had any cortical venous drainage (CVD) (OR = 3.8, p = 0.003) or convexity or torcula location (OR = 3.3, p = 0.017) were more likely to present with hemorrhage in multivariate analysis. Half of the patients had prior treatment (49.7%). Post-GRKS hemorrhage occurred in 4 patients, with an overall annual risk of 0.84% during the latency period. The annual risks of post-GKRS hemorrhage for Borden type 2–3 dAVFs and Borden type 2–3 hemorrhagic dAVFs were 1.45% and 0.93%, respectively. No hemorrhage occurred after radiological confirmation of obliteration. Independent predictors of hemorrhage following GKRS included nonhemorrhagic neural deficit presentation (HR = 21.6, p = 0.027) and increasing number of past endovascular treatments (HR = 1.81, p = 0.036).

CONCLUSIONS

Patients have similar rates of hemorrhage before and after radiosurgery until obliteration is achieved. dAVFs that have any CVD or are located in the convexity or torcula were more likely to present with hemorrhage. Patients presenting with nonhemorrhagic neural deficits and a history of endovascular treatments had higher risks of post-GKRS hemorrhage.