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Peng Xu, Wei-Ming Gong, Yao Li, Tao Zhang, Kai Zhang, De-Zhen Yin and Tang-Hong Jia

Object

Chronic mechanical compression of the spinal cord, which is commonly caused by degeneration of the spine, impairs motor and sensory functions insidiously and progressively. Yet the exact mechanisms of chronic spinal cord compression (SCC) remain to be elucidated. To study the pathophysiology of this condition, the authors developed a simple animal experimental model that reproduced the clinical course of mechanical compression of the spinal cord.

Methods

A custom-designed compression device was implanted on the exposed spinal cord of female Wistar rats between the T-7 and T-9 vertebrae. A root canal screw attached to a plastic plate was tightened 1 complete turn (1 pitch) every 7 days for 6 weeks. The placement of the compression device and the degree of compression were validated every week using radiography. Furthermore, a motor sensory deficit index was also calculated every week. After 3, 6, 9, or 12 weeks, the compressed T7–9 spinal cords were harvested and examined histologically.

Results

Lateral projection of the thoracic spine showed a progressively increasing rate of mean spinal cord narrowing in the compression group. Motor and sensory deficiencies were observed from Week 3 onward; paralysis was observed in 2 rats at Week 12. Motor deficiency appeared earlier than sensory deficiency. Obvious pathological changes were observed starting at Week 6. The number of neurons in the gray matter of rats with chronic compression of the spinal cord decreased progressively in the 6- and 9-week compression groups. In the white matter, myelin destruction and loss of axons and glia were noted. The number of terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate nick-end labeling (TUNEL)–positive neurons increased in the ventral-to-dorsal direction. The number of TUNEL-positive cells increased from Week 6 onward and peaked at Week 9.

Conclusions

This practical model accurately reproduces characteristic features of clinical chronic SCC, including progressive motor and sensory disturbances after a latency and insidious neuronal loss.

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Ya-Bin Ji, Yong-Ming Wu, Zhong Ji, Wei Song, Sui-Yi Xu, Yao Wang and Su-Yue Pan

Object

Intracarotid artery cold saline infusion (ICSI) is an effective method for protecting brain tissue, but its use is limited because of undesirable secondary effects, such as severe decreases in hematocrit levels, as well as its relatively brief duration. In this study, the authors describe and investigate the effects of a novel ICSI pattern (interrupted ICSI) relative to the traditional method (uninterrupted ICSI).

Methods

Ischemic strokes were induced in 85 male Sprague-Dawley rats by occluding the middle cerebral artery for 3 hours using an intraluminal filament. Uninterrupted infusion groups received an infusion at 15 ml/hour for 30 minutes continuously. The same infusion speed was used in the interrupted infusion groups, but the whole duration was divided into trisections, and there was a 20-minute interval without infusion between sections. Forty-eight hours after reperfusion, H & E and silver nitrate staining were utilized for morphological assessment. Infarct sizes and brain water contents were determined using H & E staining and the dry-wet weight method, respectively. Levels of neuron-specific enolase (NSE), S100β protein, and matrix metalloproteinase 9 (MMP-9) in the serum were determined using enzyme-linked immunosorbent assay. Neurological deficits were also evaluated.

Results

Histology showed that interrupted ICSI did not affect neurons or fibers in rat brains, which suggests that this method is safe for brain tissues with ischemia. The duration of hypothermia induced by interrupted ICSI was longer than that induced via the traditional method, and the decrease in hematocrit levels was less pronounced. There were no differences in infarct size or brain water content between uninterrupted and interrupted ICSI groups, but neuron-specific enolase and matrix metalloproteinase 9 serum levels were more reduced after interrupted ICSI than after the traditional method.

Conclusions

Interrupted ICSI is a safe method. Compared with traditional ICSI, the interrupted method has a longer duration of hypothermia and less effect on hematocrit and offers more potentially improved neuroprotection, thereby making it more attractive as an infusion technique in the clinic.

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Yong Hu, Christopher K. Kepler, Todd J. Albert, Zhen-shan Yuan, Wei-hu Ma, Yong-jie Gu and Rong-ming Xu

Object

The aims of this study were to evaluate a large series of posterior C-1 lateral mass screws (LMSs) to determine accuracy based on CT scanning findings and to assess the perioperative complication rate related to errant screw placement.

Methods

Accuracy of screw placement was evaluated using postoperative CT scans obtained in 196 patients with atlantoaxial instability. Radiographic analysis included measurement of preoperative and postoperative CT scans to evaluate relevant anatomy and classify accuracy of instrumentation placement. Screws were graded using the following definitions: Type I, screw threads completely within the bone (ideal); Type II, less than half the diameter of the screw violates the surrounding cortex (safe); and Type III, clear violation of transverse foramen or spinal canal (unacceptable).

Results

A total of 390 C-1 LMSs were placed, but 32 screws (8.2%) were excluded from accuracy measurements because of a lack of postoperative CT scans; patients in these cases were still included in the assessment of potential clinical complications based on clinical records. Of the 358 evaluable screws with postoperative CT scanning, 85.5% of screws (Type I) were rated as being in the ideal position, 11.7% of screws (Type II) were rated as occupying a safe position, and 10 screws (2.8%) were unacceptable (Type III). Overall, 97.2% of screws were rated Type I or II. Of the 10 screws that were unacceptable on postoperative CT scans, there were no known associated neurological or vertebral artery (VA) injuries. Seven unacceptable screws erred medially into the spinal canal, and 2 patients underwent revision surgery for medial screws. In 2 patients, unilateral C-1 LMSs penetrated the C-1 anterior cortex by approximately 4 mm. Neither patient with anterior C-1 penetration had evidence of internal carotid artery or hypoglossal nerve injury. Computed tomography scanning showed partial entry of C-1 LMSs into the VA foramen of C-1 in 10 cases; no occlusion, associated aneurysm, or fistula of the VA was found. Two patients complained of postoperative occipital neuralgia. This was transient in one patient and resolved by 2 months after surgery. The second patient developed persistent neuralgia, which remained 2 years after surgery, necessitating referral to the pain service.

Conclusions

The technique for freehand C-1 LMS fixation appears to be safe and effective without intraoperative fluoroscopy guidance. Preoperative planning and determination of the ideal screw insertion point, the ideal trajectory, and screw length are the most important considerations. In addition, fewer malpositioned screws were inserted as the study progressed, suggesting a learning curve to the technique.

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Xu-Yun Hua, Bin Liu, Yan-Qun Qiu, Wei-Jun Tang, Wen-Dong Xu, Han-Qiu Liu, Jian-Guang Xu and Yu-Dong Gu

Object

Contralateral C-7 nerve transfer was developed for the treatment of patients with brachial plexus avulsion injury (BPAI). In the surgical procedure the affected recipient nerve is connected to the ipsilateral motor cortex, and the dramatic peripheral alteration may trigger extensive cortical reorganization. However, little is known about the long-term results after such specific nerve transfers. The purpose of this study was to investigate the long-term cortical adaptive plasticity after BPAI and contralateral C-7 nerve transfer.

Methods

In this study, 9 healthy male volunteers and 5 male patients who suffered from right-sided BPAI and had undergone contralateral C-7-transfer more than 5 years earlier were included. Functional MRI studies were used for the investigation of long-term cerebral plasticity.

Results

The neuroimaging results suggested that the ongoing cortical remodeling process after contralateral C-7 nerve transfer could last for a long period; at least for 5 years. The motor control of the reinnervated limb may finally transfer from the ipsilateral to the contralateral hemisphere exclusively, instead of the bilateral neural network activation.

Conclusions

The authors believe that the cortical remodeling may last for a long period after peripheral rearrangement and that the successful cortical transfer is the foundation of the independent motor recovery.

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Jian Shen, Jian-Wei Pan, Zuo-Xu Fan, Xiao-Xing Xiong and Ren-Ya Zhan

Object

Clazosentan therapy after aneurysmal subarachnoid hemorrhage (SAH) has been found to be effective in reducing the incidence of vasospasm in randomized controlled trials. However, while vasospasm-related morbidity, including delayed ischemic neurological deficits (DINDs) and delayed cerebral infarctions, was consistently decreased, statistical significance was not demonstrated and outcomes were not affected by clazosentan treatment. The objective of this meta-analysis was to determine whether clazosentan treatment after aneurysmal SAH significantly reduced the incidence of DINDs and delayed cerebral infarctions and improved outcomes.

Methods

All randomized controlled trials investigating the effect of clazosentan were retrieved via searches with sensitive and specific terms. Six variables were abstracted after the assessment of the methodological quality of the trials. Analyses were performed following the method guidelines of the Cochrane Back Review Group.

Results

Four randomized, placebo-controlled trials met eligibility criteria, enrolling a total of 2181 patients. The meta-analysis demonstrated a significant decrease in the incidence of DINDs (relative risk [RR] 0.76 [95% CI 0.62–0.92]) and delayed cerebral infarction (RR 0.79 [95% CI 0.63–1.00]) in patients treated with clazosentan after aneurysmal SAH. However, this treatment regimen was not shown to outcomes including functional outcomes measured by Glasgow Outcome Scale-Extended (RR 1.12 [95% CI 0.96–1.30]) or mortality (RR 1.02 [95%CI 0.70–1.49]). Adverse events, including pulmonary complications, anemia, and hypotension, were all significantly increased in patients who received clazosentan therapy.

Conclusions

The results of the present meta-analysis show that treatment with clazosentan after aneurysmal SAH significantly reduced the incidence of the vasospasm-related DINDs and delayed cerebral infarctions, but did not improve poor neurological outcomes in patients with aneurysmal SAH. Further study is required to elucidate the dissociation between vasospasm-related morbidity and outcomes.

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Hanqiang Jiang, Wei Ni, Bin Xu, Yu Lei, Yanlong Tian, Feng Xu, Yuxiang Gu and Ying Mao

Object

The outcome of patients with hemorrhagic moyamoya disease (MMD) after cerebral revascularization is uncertain. The purpose of this study was to delineate the efficacy of this surgical method in the treatment of hemorrhagic MMD.

Methods

Between January 2007 and August 2011, a consecutive cohort of 113 patients with hemorrhagic MMD was enrolled into this prospective single-center cohort study. The surgical method was combined direct and indirect bypass. The cumulative probability of the primary end point (all stroke and deaths from surgery through 30 days after surgery and ipsilateral recurrent hemorrhage afterward) was analyzed. The angiographic outcome was measured by the following parameters: bypass patency, reduction of basal MMD vessels, improved degree of dilation, and branch extension of the anterior choroidal and posterior communicating arteries (AChA-PCoA).

Results

Of the 113 enrolled cases, CT scans revealed pure intraventricular hemorrhage (IVH) in 63 cases (55.7%), pure intracranial hemorrhage (ICH) in 14 cases (12.4%), and ICH with IVH in 36 cases (31.9%). In 74 of 113 hemorrhagic hemispheres (65.5%), the AChA-PCoA was extremely dilated with extensive branches beyond the choroidal fissure. A total of 114 surgeries were performed. No patient suffered ischemic or hemorrhagic stroke through 30 days after surgery. Ipsilateral rebleeding occurred in 5 patients, 4 of whom died of the rebleeding event. The cumulative probability of the primary end point was 0% at 1 year and 1.9% at 2 years. The annual rebleeding rate was 1.87%/person/year. The improvement in AChA-PCoA extension was observed in 75 of 107 operated hemispheres (70.1%), which was higher than that in 7 of 105 unoperated hemispheres (35.2%).

Conclusions

Revascularization may provide a benefit over conservative therapy for hemorrhagic MMD patients. The improvement of dilation and branch extension of AChA-PCoA might be correlated with the low rebleeding rate.

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Isabelle Thibault, Ameen Al-Omair, Giuseppina Laura Masucci, Laurence Masson-Côté, Fiona Lochray, Renée Korol, Lu Cheng, Wei Xu, Albert Yee, Michael G. Fehlings, Georg A. Bjarnason and Arjun Sahgal

Object

The aim of this study was to evaluate local control (LC) and the risk of vertebral compression fracture (VCF) after stereotactic body radiotherapy (SBRT) in patients with renal cell cancer spinal metastases.

Methods

Prospectively collected data on 71 spinal segments treated with SBRT in 37 patients were reviewed. The median follow-up was 12.3 months (range 1.2–55.4 months). The LC rate was assessed based on each spinal segment treated and overall survival (OS) according to each patient treated. Sixty of 71 segments (85%) were radiation naive, 11 of 71 (15%) were previously irradiated, and 10 of 71 (14%) were treated with postoperative SBRT. The median SBRT total dose and number of fractions were 24 Gy and 2, respectively. The VCF analysis also included evaluation of the Spinal Instability Neoplastic Score criteria.

Results

The 1-year OS and LC rates were 64% and 83%, respectively. Multivariate analysis identified oligometastatic disease (13 of 37 patients) as a positive prognostic factor (p = 0.018) for OS. Of 61 non-postoperative spinal segments treated, 10 (16%) developed VCFs; 3 of 10 were de novo VCFs and 7 of 10 occurred as progression of an existing VCF. The 1-year VCF-free probability rate was 82%. Multivariate analysis identified single-fraction SBRT and baseline VCF as significant predictors of SBRT-induced VCF (p = 0.028 and p = 0.012, respectively).

Conclusions

Spine SBRT yields high rates of local tumor control in patients with renal cell cancer. Baseline VCF and 18–24 Gy delivered in a single fraction were predictive of further collapse. Patients with oligometastatic disease may benefit most from such aggressive local therapy, given the prolonged survival observed.