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Michael Zhang, Yi-Ren Chen, Steven D. Chang and Anand Veeravagu

OBJECTIVE

Symptomatic vertebral hemangiomas (SVHs) are a very rare pathology that can present with persistent pain or neurological deficits that warrant surgical intervention. Given the relative rarity and difficulty in assessment, the authors sought to present a dedicated series of SVHs treated using stereotactic radiosurgery (SRS) to provide insight into clinical decision making.

METHODS

A retrospective review of a single institution's experience with hypofractionated radiosurgery for SVH from 2004 to 2011 was conducted to determine the clinical and radiographic outcomes following SRS treatment. The authors report and analyze the treatment course of 5 patients with 7 lesions, 2 of which were treated primarily by SRS.

RESULTS

Of the 5 patients studied, 4 presented with a chief complaint of pain refractory to conservative measures. Three patients reported dysesthesias, and 2 reported upper-extremity weakness. Following radiosurgery, 4 of 5 patients exhibited improvement in their primary symptoms (3 for pain and 1 for weakness), achieving a clinical response after a mean period of 1 year. In 2 cases there was 20%–40% reduction in lesion size in the most responsive dimension as noted on images. All treatments were well tolerated.

CONCLUSIONS

SRS for SVH is a safe and feasible treatment strategy, comparable to prior radiotherapy studies, and in select cases may successfully confer delayed decompressive effects. Additional investigation will determine future patient selection and how conformal SRS treatment can best be administered.

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Lei Zhang, Zhiqiang Yi, Hongzhou Duan and Liang Li

OBJECTIVE

The purpose of this study was to introduce a novel autologous duraplasty procedure for the treatment of Chiari malformation Type I (CM-I).

METHODS

The authors retrospectively reviewed data from patients who had been diagnosed with CM-I and had undergone suboccipital decompression and autologous duraplasty in situ or synthetic dural graft duraplasty; patients were treated in the authors' department between 2011 and 2014. All procedures were performed by the same surgeon. The 2 duraplasty methods were compared in terms of surgical factors and complications. The authors assessed the neurological outcome and MRI-documented syrinx size at the 6-month follow-up visit.

RESULTS

Twenty-seven patients were enrolled in this study, 13 in the duraplasty in situ group and 14 in the synthetic dural graft duraplasty group. The results showed no significant differences between the duraplasty in situ and synthetic dural graft duraplasty groups in overall operative time (4.9 hours vs 4.1 hours; p = 0.070), estimated blood loss (229 ml vs 254 ml; p = 0.159), and duration of hospital stay after the operation (13.5 days vs 12.8 days; p = 0.808). In the duraplasty in situ group, 1 case of meningitis occurred (7.7%). In the synthetic dural graft duraplasty group, the complications included 1 case of meningitis (7.1%) and 1 CSF leak (7.1%). The mean cost of hospitalization in the duraplasty in situ group (CNY 23,354) was significantly lower than that in the synthetic dural graft duraplasty group (CNY 29,385; p = 0.036).

CONCLUSIONS

Compared with synthetic dural graft duraplasty, autologous duraplasty in situ is a safe, effective, and cost-effective procedure for the treatment of CM-I. The long-term outcome of this procedure requires investigation.

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Yanlu Zhang, Michael Chopp, Zheng Gang Zhang, Yi Zhang, Li Zhang, Mei Lu, Talan Zhang, Stefan Winter, Hemma Brandstätter, Asim Mahmood and Ye Xiong

OBJECTIVE

Cerebrolysin is a neuropeptide preparation that mimics the properties of neurotrophic factors and has had beneficial effects in the treatment of neurodegenerative diseases, stroke, and traumatic brain injury (TBI). To further evaluate treatment schemes, the authors assessed the dose-response of Cerebrolysin on functional improvement in a rat model of mild TBI (mTBI).

METHODS

This dose-response study was a prospective, randomized, blinded, and placebo-controlled preclinical experiment. Male Wistar adult rats, subjected to mTBI induced by a closed head impact, were treated randomly with 0 (saline as placebo), 0.8, 2.5, or 7.5 ml/kg of Cerebrolysin 4 hours after mTBI and daily for a total of 10 consecutive days. A battery of cognitive and sensorimotor functional tests was performed over 90 days.

RESULTS

The primary outcome was functional improvement over the 90 days; animal weight and death were the secondary and safety outcomes, respectively. A significant (p < 0.001) dose effect of Cerebrolysin on cognitive recovery 3 months after injury was found. Cerebrolysin at a dose of ≥ 0.8 ml/kg significantly (p < 0.001) improved cognitive outcome. The higher dose (7.5 ml/kg) resulted in significantly better cognitive recovery than the lowest doses (0.8 ml/kg) but not relative to the 2.5-ml/kg dose. Cerebrolysin at a dose of 2.5 or 7.5 ml/kg also caused different onset times of significant improvement in sensorimotor function. No differences in body weight or mortality rate among the groups were found.

CONCLUSIONS

This preclinical randomized, placebo-controlled, and blinded study with a clinically relevant treatment scheme revealed that Cerebrolysin at doses of 0.8–7.5 ml/kg, administered 4 hours after mTBI and then once daily for a total of 10 consecutive days, improved functional outcomes 3 months after injury. A dose of 2.5 ml/kg is likely an optimal dose for the treatment of experimental mTBI.

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Yanlu Zhang, Michael Chopp, Yi Zhang, Zheng Gang Zhang, Mei Lu, Talan Zhang, Kuan-Han H. Wu, Li Zhang, Asim Mahmood and Ye Xiong

OBJECTIVE

The authors previously demonstrated that Cerebrolysin is effective for treatment of mild closed head injury (CHI) when administered 4 hours after injury. The aim of this study was to determine Cerebrolysin’s effects on functional and histological outcomes in rats subjected to moderate CHI.

METHODS

In this randomized, blinded, and vehicle-controlled preclinical trial, male adult Wistar rats subjected to moderate CHI received either Cerebrolysin treatment at a dose of 2.5 ml/kg (n = 13) or vehicle (saline, n = 13) intraperitoneally administered daily for 10 days, starting at 4 hours after injury. Animals were subjected to cognitive and sensorimotor functional tests at multiple time points, and they were killed 3 months after injury. The brains were processed for analyses of neuronal cell loss, amyloid precursor protein, axonal damage, and neurogenesis.

RESULTS

Compared with rats treated with vehicle (saline), rats treated with Cerebrolysin had significantly increased numbers of neuroblasts and newborn mature neurons in the dentate gyrus (DG) and attenuated amyloid precursor protein accumulation and axonal damage in various brain regions, as well as decreased neuronal loss in the DG and cornu ammonis 3 (CA3) region of the hippocampus (p < 0.05). Global testing using generalized estimating equations showed a significant beneficial effect of Cerebrolysin treatment on sensorimotor functional outcomes from 1 day to 3 months after injury compared to that of saline treatment (p < 0.05). Compared with vehicle-treated rats, Cerebrolysin-treated rats showed significantly and robustly improved long-term (up to 3 months) cognitive functional recovery, as measured by social interaction, Morris water maze, novel object recognition, and odor recognition tests. In the Cerebrolysin-treated rats there were significant correlations between multiple histological outcomes and functional recovery evident 3 months after moderate CHI, as indicated by Pearson partial correlation analyses.

CONCLUSIONS

The authors’ findings demonstrate that Cerebrolysin treatment significantly improves long-term functional and histological outcomes in rats with moderate CHI, with functional outcomes significantly correlated with histological indices of neuroplasticity and neuroprotection. These data indicate that Cerebrolysin may be useful for the treatment of moderate CHI.

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Jian-Bin Chen, Ding Lei, Min He, Hong Sun, Yi Liu, Heng Zhang, Chao You and Liang-Xue Zhou

OBJECT

The present study aimed to clarify the incidence and clinical features of disease progression in adult moyamoya disease (MMD) patients with Graves disease (GD) for better management of these patients.

METHODS

During the past 18 years, 320 adult Chinese patients at West China Hospital were diagnosed with MMD, and 29 were also diagnosed with GD. A total of 170 patients (25 with GD; 145 without GD) were included in this study and were followed up. The mean follow-up was 106.4 ± 48.6 months (range 6–216 months). The progression of the occlusive lesions in the major intracranial arteries was measured using cerebral angiography and was evaluated according to Suzuki's angiographic staging. Information about cerebrovascular strokes was obtained from the records of patients' recent clinical visits. Both angiographic progression and strokes were analyzed to estimate the incidences of angiographic progression and strokes using Kaplan-Meier analysis. A multivariate logistic regression model was used to test the effects of sex, age at MMD onset, disease type, strokes, and GD on the onset of MMD progression during follow-up.

RESULTS

During follow-up, the incidence of disease progression in MMD patients with GD was significantly higher than in patients without GD (40.0% vs 20.7%, respectively; p = 0.036). The interval between initial diagnosis and disease progression was significantly shorter in MMD patients with GD than in patients without GD (p = 0.041). Disease progression occurred in both unilateral MMD and bilateral MMD, but the interval before disease progression in patients with unilateral disease was significantly longer than in patients with bilateral disease (p = 0.021). The incidence of strokes in MMD patients with GD was significantly higher than in patients without GD (48% vs 26.2%, respectively; p = 0.027). The Kaplan-Meier survival curve showed significant differences in the incidence of disease progression (p = 0.038, log-rank test) and strokes (p = 0.031, log-rank test) between MMD patients with GD and those without GD. Multivariate analysis suggested that GD may contribute to disease progression in MMD (OR 5.97, 95% CI 1.24–33.76, p = 0.043).

CONCLUSIONS

The incidence of disease progression in MMD patients with GD was significantly higher than that in MMD patients without GD, and GD may contribute to disease progression in MMD patients. The incidence of strokes was significantly higher in MMD patients with GD than in patients without GD. Management guidelines for MMD patients with GD should be developed.

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Dunyue Lu, Asim Mahmood, Ruilan Zhang, Yi Li and Michael Chopp

Object. Neurogenesis, which is upregulated by neural injury in the adult mammalian brain, may be involved in the repair of the injured brain and functional recovery. Therefore, the authors sought to identify agents that can enhance neurogenesis after brain injury, and they report that (Z)-1-[N-(2-aminoethyl)-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA/NONOate), a nitric oxide donor, upregulates neurogenesis and reduces functional deficits after traumatic brain injury (TBI) in rats.

Methods. The agent DETA/NONOate (0.4 mg/kg) was injected intraperitoneally into 16 rats daily for 7 days, starting 1 day after TBI induced by controlled cortical impact. Bromodeoxyuridine (100 mg/kg) was also injected intraperitoneally daily for 14 days after TBI to label the newly generated cells in the brain. A neurological functional evaluation was performed in all rats and the animals were killed at 14 or 42 days postinjury. Immunohistochemical staining was used to identify proliferating cells.

Conclusions. Compared with control rats, the proliferation, survival, migration and differentiation of neural progenitor cells were all significantly enhanced in the hippocampus, subventricular zone, striatum, corpus callosum, and the boundary zone of the injured cortex, as well as in the contralateral hemisphere in rats with TBI that received DETA/NONOate treatment. Neurological functional outcomes in the DETA/NONOate-treated group were also significantly improved compared with the untreated group. These data indicate that DETA/NONOate may be useful in the treatment of TBI.

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He Xiao-Sheng, Yi Sheng-Yu, Zhang Xiang, Fei Zhou, Zhang Jian-Ning and Yang Li-Sun

Object. The authors investigated the ramifications of producing diffuse axonal injury (DAI) by lateral head rotation in a rat model.

Methods. Using a special injury-producing device, the rat's head was rapidly rotated 90° in the coronal plane at an angular velocity of at least 753.13 rad/second and an angular acceleration of at least 1.806 × 105 rad/second2; the rotation was complete within 2.09 msec. There were no statistically significant changes in PO2, PCO2, pH, or blood pressure values at 5, 15, or 60 minutes after head rotation compared with their respective preinjury baseline values. The rats exhibited posttraumatic behavior suppression for an average of 12.6 minutes. The mortality rate was 17%. The rats that survived had diffuse subarachnoid hemorrhage around the brainstem and upper cervical cord, but no obvious brain contusion. In sections stained with silver or hematoxylin and eosin, axonal swelling and bulblike protrusions at the axonal axis were observed in the medulla oblongata, midbrain, upper cervical cord, and corpus callosum between 6 hours and 144 hours postinjury. The axonal injuries were most severe in the brainstem and were accompanied by parenchymal bleeding. The density of bulblike axonal protrusions peaked 6 hours postinjury in the medulla oblongata and 24 hours postinjury in the midbrain.

Conclusions. Rapid lateral head rotation can produce DAI characterized by severe damage to the rat brainstem.

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Xiaowei Li, Zhaosheng Sun, Wangmiao Zhao, Jinrong Zhang, Jianchao Chen, Yongqian Li, Yanqiao Ye, Jinlian Zhao, Xuehui Yang, Yi Xiang, Guangjie Li, Jianhui Mao, Wenchao Zhang, Mingzhe Zhang and Wanzeng Zhang

Object

The authors evaluated the effects of acetylsalicylic acid (ASA) usage and transfusion of previously frozen apheresis platelets on postoperative hemorrhage, activities of daily living (ADL) score, and mortality rate in patients with acute hypertensive basal ganglia hemorrhage undergoing craniotomy.

Methods

This was a prospective, double-blind, parallel, randomized controlled trial in patients with acute hypertensive basal ganglia hemorrhage, who had either not received ASA therapy (control) or received ASA therapy. The patients who received ASA therapy were divided according to the results of a platelet aggregation test into ASA-resistant, ASA-semiresponsive, and ASA-sensitive groups. All patients required an emergency craniotomy for hematoma removal after hospitalization. The patients who were sensitive to ASA were randomized to receive one of the following transfusion regimens of previously frozen apheresis platelets: no transfusion, 1 therapeutic dose before surgery, or 2 therapeutic doses (1 before surgery and 1 after 24 hours of hospitalization). The postoperative hemorrhage rate and the average postoperative hemorrhage volume were recorded and the ADL scores and mortality rate were measured during a 6-month follow-up period.

Results

The rate of postoperative hemorrhage, average postoperative hemorrhage volume, and mortality rate were significantly higher in the ASA-sensitive patients who received ASA therapy compared with patients who did not receive ASA therapy (all p < 0.005). The ADL scores were grouped into different grades and the number of cases in the lower grades was higher and the overall scores were poorer in patients who received ASA therapy compared with those who did not (all p < 0.005). After transfusion of previously frozen apheresis platelets, the postoperative hemorrhage rate, average postoperative hemorrhage volume, and mortality rate of the ASA-sensitive patients were significantly lowered (all p < 0.005), and the ADL scores and their classification level were better than those of patients who did not undergo transfusion (all p < 0.005).

Conclusions

Transfusion of previously frozen apheresis platelets reduces the rate of postoperative hemorrhage, average postoperative hemorrhage volume, disability rate, and mortality rate in ASA-sensitive patients with acute hypertensive basal ganglia hemorrhage undergoing craniotomy.

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Jun Pan, Songtao Qi, Yi Liu, Yuntao Lu, Junxiang Peng, XiAn Zhang, YiKai Xu, Guang-long Huang and Jun Fan

OBJECT

Craniopharyngiomas (CPs) are rare epithelial tumors that are often associated with an enigmatic and unpredictable growth pattern. Understanding the growth patterns of these tumors has a direct impact on surgical planning and may enhance the safety of radical tumor removal. The aim of this study was to analyze the growth patterns and surgical treatment of CPs with a focus on the involvement of the hypothalamopituitary axis and the relationship of the tumor to the arachnoid membrane and surrounding structures.

METHODS

Clinical data from 226 consecutive patients with primary CP were retrospectively reviewed. Tumor location and the relationship of the tumor to the third ventricle floor and the pituitary stalk were evaluated using preoperative MRI and intraoperative findings. A topographic classification scheme was proposed based on the site of tumor origin and tumor development. The clinical relevance of this classification on patient presentation and outcomes was also analyzed.

RESULTS

The growth of CPs can be broadly divided into 3 groups based on the site of tumor origin and on tumor-meningeal relationships: Group I, infrasellar/infradiaphragmatic CPs (Id-CPs), which mainly occurred in children; Group II, suprasellar subarachnoid extraventricular CPs (Sa-CPs), which were mainly observed in adults and rarely occurred in children; and Group III, suprasellar subpial ventricular CPs (Sp-CPs), which commonly occurred in both adults and children. Tumors in each group may develop complex growth patterns during vertical expansion along the pituitary stalk. Tumor growth patterns were closely related to both clinical presentation and outcomes. Patients with Sp-CPs had more prevalent weight gain than patients with Id-CPs or Sa-CPs; the rates of significant weight gain were 41.7% for children and 16.7% for adults with Sp-CPs, 2.2% and 7.1% for those with Id-CPs, and 12.5% and 2.6% for those with Sa-CPs (p < 0.001). Moreover, patients with Sp-CPs had increased hypothalamic dysfunction after radical removal; 39% of patients with Sp-CPs, 14.5% with Id-CPs, and 17.4% with Sa-CPs had high-grade hypothalamic dysfunction in the first 2 postoperative years (p < 0.001).

CONCLUSIONS

The classification of CPs based on growth pattern may elucidate the best course of treatment for this formidable tumor. More tailored, individualized surgical strategies based on tumor growth patterns are mandatory to provide long-term tumor control and to minimize damage to hypothalamic structures. Differences in the distribution of growth patterns between children and adults imply that hierarchical comparison is necessary when investigating outcomes and survival across treatment paradigms in patients with CP.

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Yi Ping Zhang, Christopher Iannotti, Lisa B. E. Shields, Yingchun Han, Darlene A. Burke, Xiao-Ming Xu and Christopher B. Shields

Object. Laceration-induced spinal cord injury (SCI) results in the invasion of a connective tissue scar, progressive damage to the spinal cord due to complex secondary injury mechanisms, and axonal dieback of descending motor pathways. The authors propose that preparation of the spinal cord for repair strategies should include hematoma removal and dural closure, resulting in apposition of the severed ends of the spinal cord. Such procedures may reduce the size of the postinjury spinal cord cyst as well as limit scar formation.

Methods. Using a novel device, the Vibraknife, the authors created a dorsal hemisection of the spinal cord at C-6 in the adult rat. In Group 1 (eight rats), the dura mater was repaired with apposition of the two stumps of the spinal cord to reduce the lesion gap. In Group 2 (10 rats), the dura was not closed and the two cord stumps were not approximated. All rats were killed at 4 weeks postinjury, and the spinal cords from each group were removed and examined using histological, stereological, and immunohistochemical methods.

In Group 1 rats a significant reduction of the total lesion volume and connective tissue scar was observed compared with those in Group 2 (Student t-test, p < 0.05). Approximation of the stumps did not promote the regeneration of corticospinal tract fibers or sensory axons through the lesion site.

Conclusions. Apposition of the severed ends of the spinal cord by dural closure reduces the lesion gap, cystic cavitation, and connective tissue scar formation. These outcomes may collectively reduce secondary tissue damage at the injury site and shorten the length of the lesion gap, which will facilitate transplantation-mediated axonal regeneration after laceration-induced SCI.