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Introduction: Early surgical treatment has been proposed to improve outcomes of selected patients with poor-grade ruptured intracranial aneurysms. We performed a multicenter retrospective analysis to identify complications and outcomes after early surgery., Methods: We analyzed data from the two cohorts of patients with poor-grade ruptured aneurysms. Poor-grade aneurysm was defined as a World Federation of Neurosurgical Society (WFNS) grade of IV or V after resuscitation. Early surgery was defined as surgery performed within 72 h after poor-grade condition., Results: Of the 144 patients who underwent surgical treatment for poor-grade aneurysm, 80 underwent early surgery and were included in this report. Forty-one (51%) patients presented with a WFNS grade of IV and 39 (49%) presented with a WFNS grade of V. Cerebral infarction occurred in 17 (21%) patients and was the most common complication except for pneumonia. No patients had a good outcome after postoperative aneurysm rebleeding. At follow-up (mean 12.6 months), 37 (46%) patients had a good outcome after early surgery. Multivariate analysis showed that a WFNS grade of V, presence of intraventricular hemorrhage, brain herniation were independent predictors of poor outcome after early surgery. Patients with WFNS grade V more often had a poor outcome after postoperative cerebral infarction, rebleeding or symptomatic vasospasm., Conclusions: Patients with a WFNS grade of V, intraventricular hemorrhage, brain herniation were more likely to have a poor outcome after early surgery. Postoperative complications, including rebleeding and cerebral infraction, should be prevented and treated aggressively to maximize the chance of good outcome in poor-grade patients., (Copyright © 2015 IJS Publishing Group Limited. Published by Elsevier Ltd. All rights reserved.)

Objective: We reviewed our prospective study of patients with occipital arteriovenous malformations (AVMs) to assess whether the display of optic radiation diffusion tensor imaging (DTI) during neuronavigation-guided surgery can reduce the severity of postoperative visual field deficits (VFDs) and to evaluate the factors associated with visual field preservation., Methods: Forty-six consecutive patients with occipital AVMs were randomized in our study. DTI of the optic radiation was displayed during neuronavigation surgery in 24 patients. The other 22 patients were treated surgically without neuronavigation. Modified Rankin Scale (mRS) scores and visual fields were evaluated preoperatively, immediately after surgery, and at the last follow-up., Results: The patients' baseline characteristics and AVM features were statistically similar between the 2 surgical groups. The postoperative obliteration rate was 100%. The postoperative mRS scores did not differ between the 2 groups (P > 0.05). Preexisting VFDs were more common (P = 0.00004) in patients who bled than in those with unruptured AVMs. The application of DTI-incorporated neuronavigation reduced the frequency and severity of postoperative VFDs (P = 0.013 and 0.001, respectively). Visual fields were more likely to be preserved in patients with an AVM >5 mm from the optic radiation (P = 0.025)., Conclusions: A history of hemorrhage is an independent risk factor for VFDs associated with occipital AVMs. Although not showing superiority in postoperative mRS, functional MRI navigation-guided surgery may help to radically resect occipital AVMs and preserve patient visual fields. A 5-mm distance from the optic radiation may be a suitable safety margin for visual field preservation., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: In this aging society, attention has not been fully given to brain arteriovenous malformations (AVMs) in elderly patients. This study sought to describe a single institution's experience treating arteriovenous malformations (AVMs) in elderly patients., Methods: We conducted a retrospective review of brain AVMs in elderly patients treated at our institution between 1990 and 2012 with a focus on the clinical features, risk of hemorrhage and treatment outcomes., Results: Of the 2790 patients in our AVM database, 98 patients were over the age of 60 at presentation. Forty-eight percent presented with hemorrhage. Risks of initial hemorrhage were history of hypertension, smaller AVM size (<3 cm) and exclusively deep venous drainage. Treatment modalities were microsurgical resection in 65 %, embolization alone in 10 %, stereotactic radiosurgery (SRS) in 11 % and observation in 14 %. Preoperative embolization was performed in 32 % in the surgical group. Complete obliteration was achieved in 95 % by microsurgery, 30 % by embolization alone and 45 % by SRS. Good functional outcome (modified Rankin Scale, mRS <2) was achieved in 69 % after a median follow-up of 5.8 years. Multivariate logistic analysis revealed that a pretreatment mRS score ≥2, eloquent location and higher S-M grade (IV or V) were associated with worsening functional status, whereas surgical resection was a negative factor. Posttreatment hemorrhage occurred in 8 %. AVM-related death occurred in three patients (2 by surgery and 1 by observation)., Conclusions: Brain AVMs in elderly patients still pose a high risk of hemorrhage. Initial hemorrhage may be associated with a history of hypertension, AVM size and exclusively deep venous drainage. Initial mRS score ≥2, eloquent location and higher S-M grade may be associated with worsening functional status. Microsurgical resection can be safe and effective for selected patients. Preoperative embolization is helpful in patients with S-M grade IV-V AVMs. For those with surgical contraindications, SRS and observation are treatment alternatives.

Objectives: Rebleeding is an unsatisfactory outcome for patients with haemorrhagic MMD. This study mainly investigated clinical features and outcomes in haemorrhagic MMD., Methods: A retrospective review was performed on a total of 154 patients with haemorrhagic MMD comprising 126 surgically treated and 28 conservatively treated patients., Results: There were 102 female and 52 male patients with a mean age at the initial bleeding of 33.95 years. Preoperative rebleeding occurred in 37 patients, and multivariate Cox regression analysis demonstrated that age at the time of initial bleeding (P < 0.001, HR = 1.093) was a risk factor for preoperative rebleeding. Of 124 patients with surgical revascularization, perioperative ischaemic stroke occurred in five (4.03%) and intracranial bleeding in four (3.23%). The mean follow-up period was 36.12  months. Recurrent bleeding occurred in six (10.17%) of 59 patients treated with direct revascularization, seven (20.69%) of 34 patients treated with indirect revascularization, two (6.45%) of 31 patients treated with combined revascularization and six (21.43%) of 28 patients treated conservatively. Kaplan-Meier analysis revealed no statistical differences in preventing rebleeding between direct, indirect and combined revascularization and conservative treatment (P = 0.311)., Conclusions: Age at the initial bleeding is a risk factor for rebleeding in haemorrhagic MMD. Although surgical revascularization show the tendency to decrease the rebleeding rate, there is no statistical difference between direct revascularization, indirect revascularization, combined revascularization and conservative treatment in preventing rebleeding. Further study is needed to determine whether surgical revascularization is effective in select population or with certain techniques.

Objective: The goal of this study was to discuss the surgical indications, surgical approaches, and prognostic factors of cerebellar cavernous malformation (CM)., Methods: We retrospectively reviewed the presentation, surgery, and outcome of 58 consecutive patients who underwent resection of cerebellar CMs between 2009 and 2013 in our center., Results: The study population consisted of 31 males and 27 females, mean age 39.9 years. Fifty-eight patients experienced 67 symptomatic hemorrhages. The median diameter of all lesions was 2.2 ± 0.9 cm (range, 0.8-4.8 cm). The locations were classified into 3 groups: group 1, cerebellar hemisphere (17 cases, 29.3%); group 2, vermis (18 cases, 31.0%); and group 3, cerebellar peduncle (23 cases, 39.7%). Complete resection was achieved in all patients without surgical mortality. Postoperatively, 11 patients developed new surgical complications, including facial paralysis in 6 patients, ataxia in 2 patients, dizziness in 2 patients, and decrease in facial sensation in 1 patient. The mean modified Rankin Scale (mRS) at final follow-up was significantly improved compared with the preoperative score (0.5 ± 0.5 vs. 1.4 ± 0.7, P = 0.035). The symptoms and neurologic deficits improved in most patients. The lesion location was the only factor that predicted a worse outcome, and the mRS was significantly lower in group 3 than groups 1 and group 2 (P = 0.019)., Conclusions: Patients with cerebellar CMs usually achieve favorable outcomes via surgery. Cerebellar peduncle CMs cause significantly more neurologic deficits than other locations. A reasonable surgical approach and meticulous manipulation are necessary to prevent impairment of neurologic function., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Objective: A retrospective study was conducted to analyze the clinical data of patients treated by retractorless surgery and explore the clinical feasibility and practical application of this strategy., Methods: A total of 194 patients undergone retractorless surgery in Beijing Tiantan Hospital from Nov 2013 to Oct 2014 were retrospectively reviewed. Complications related to microsurgical approaches, disease types, neurological function score and intraoperative compression or stretching were analyzed., Results: Of the 194 cases, there were 127 (65%) patients with cerebrovascular diseases and 67 (35%) patients with intracranial tumors. Sixty patients had anterior circulation aneurysms, of them, 21 aneurysms were accessed through frontal-lateral approaches and 39 reached via pterional approaches. Two patients with posterior inferior cerebellar artery (PICA) aneurysms were treated by far-lateral approaches. Fifteen patients with cerebellopontine angle (CPA) tumors were treated by retrosigmoid approaches. Elven patients with supratentorial tumors were treated by anterior and posterior interhemispheric approaches. Twenty patients with posterior fossa tumors were treated by suboccipital posterior median and paramedian approaches. Two patients with petroclival region lesions were treated by subtemporal approaches. Damage of tissues surrounding the approach occurred in 4 cases (2%). One patient received secondary procedures (0.52%) and 2 patients died after operation (1%). No change of postoperative neurological function was seen in 62.3% of cases, improvement of postoperative neurological function was seen in 29.4% and neurological function deterioration 8.24%., Conclusions: Compared with the retractor surgery, retractorless surgery does not increase the rate of damage of tissues surrounding the approach. With the proficiency in micro-neurosurgery methods, retractorless surgery can reduce the postoperative complications.

Objective: Aggressive surgery seems mandatory for poor-grade middle cerebral artery (MCA) aneurysm with associated intracerebral hemorrhage (ICH). However, primary decompressive craniectomy (DC) is controversial. We performed a case control study to define the role of primary DC., Materials and Methods: We analyzed data from the two cohorts: a multicenter prospective poor-grade aSAH registry study (AMPAS); and the National Clinical Research Center for Neurological Diseases (NCRC-ND) database of poor-grade patients. Outcome was assessed by modified Rankin Scale (mRS) and was dichotomized into favorable (mRS 0-3) and unfavorable outcome (mRS 4-6). We compared major complication rates, mortality and outcomes between primary DC and control groups., Results: Twenty-four patients with primary DC were included in the study group. Fourteen patients without DC were included in the control group. Patients with younger age and lower Glasgow coma score (GCS) more often underwent primary DC. Major complications did not differ between the two groups. Fourteen (58%) patients had a favorable outcome, and the mortality was 29%. Primary DC appeared to have lower in-hospital mortality and have better outcome. Adjusting for age and admission GCS, primary DC was not significantly associated with decreased mortality and improved outcomes., Conclusions: Although primary DC does not increase postoperative complication and mortality risk, current results showed primary DC does not seem to be significantly associated with improved outcomes. However, more than one half of patients most benefit from primary DC. Further prospective controlled studies are warranted to clarify the issue., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: To determine factors and outcomes associated with ultra-early surgery for poor-grade aneurysmal subarachnoid haemorrhage (aSAH)., Design: A multicentre retrospective analysis, observational study., Setting: High-volume teaching hospitals (more than 150 aSAH cases per year)., Participants: 118 patients with World Federation of Neurosurgical Societies (WFNS) grades IV and V underwent surgical treatment. Ultra-early surgery was defined as surgery performed within 24 h of aSAH, and delayed surgery as surgery performed after 24 h. Outcome was assessed by modified Rankin Scale (mRS). The mean time of follow-up was 12.5±3.4 months (range 6-28 months)., Results: 47 (40%) patients underwent ultra-early surgery, and 71 (60%) patients underwent delayed surgery. Patients with WFNS grade V (p=0.011) and brain herniation (p=0.004) more often underwent ultra-early surgery. Postoperative complications were similar in ultra-early and delayed surgery groups. Adjusted multivariate analysis showed the outcomes were similar between the two groups. Multivariate analysis of predictors of poor outcome, ultraearly surgery was not an independent predictor of poor outcome, while advanced age, postresuscitation WFNS V grade, intraventricular haemorrhage, brain herniation and non-middle cerebral artery (MCA) aneurysms were associated with poor outcome., Conclusions: Although patients with WFNS grade V and brain herniation more often undergo ultra-early surgery, postoperative complications and outcomes in selected patients were similar in the two groups. Patients of younger age, WFNS grade IV, absence of intraventricular haemorrhage, absence of brain herniation and MCA aneurysms are more likely to have a good outcome. Ultra-early surgery could improve outcomes in carefully selected patients with poor-grade aSAH., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: To explore the expression and role of Caveolin-1 in the angiogenesis of cerebral arteriovenous malformation (AVM)., Methods: A total of 55 fresh AVM samples at Affiliated Hospital, Inner Mongolia Medical University and Beijing Tiantan Hospital from August 2013 to May 2014 were collected to test the expressions of Caveolin-1, vascular endothelial growth factor (VEGF), vascular endothelial growth factor-receptor 2 (VEGF-R2) and endothelial nitric oxide synthase (eNOS) by immunohistochemistry and Western blot. And the relationship between the expressions of Caveolin-1 and VEGF, VEGF-R2 and eNOS was analysed., Results: The expression rates of Caveolin-1, VEGF, VEGF-R2 and eNOS in human AVM were 100%, 87.27%, 76.36% and 85.45%. And the values were significantly higher than those in normal superficial temporal artery. Western blot showed that the expressions of Caveolin-1, VEGF, VEGF-R2 and eNOS in hemorrahge AVM were higher than those in non-hemorrahge counterpart (P < 0.05). The expressions of Caveolin-1, VEGF, VEGF-R2 and eNOS were consistent., Conclusion: Caveolin-1 plays a positive regulatory role in the angiogenesis of AVM through the PI3K/Akt signaling pathway. In cerebral AVM, Caveolin-1 plays an important role in occurrence, progression, hemorrahge and degradation of brain AVM.

Background and Objective: Mirror-like intracranial aneurysms (MirAn) occur symmetrically at the corresponding intracranial arteries and are a subgroup of multiple intracranial aneurysms. The aim of this study was to analyze the risk factors, treatment, and prognosis of MirAn., Methods: We retrospectively analyzed 43 cases of MirAn diagnosed between January 2000 and December 2009. The control groups comprised patients with non-mirror-like multiple aneurysms (nMirAn) and single aneurysms (SingAn). Sex, age, localization of MirAn, hypertension, diabetes, smoking, and rupture were identified as potential risk factors for MirAn., Results: The male to female ratio of the MirAn patients was 1.0:5.1, which was significantly different from that of the nMirAn patients (1.0:1.9, P=0.037) and SingAn patients (1.0:1.3, P<0.001). There was no difference in age (P=0.8741), smoking (P=0.301), diabetes (P=0.267), or hypertension (P=0.874) between the MirAn and nMirAn patients. The aneurysms in 28 MirAn patients (65.1%) involved the internal carotid-posterior communicating arteries; in these patients, the rupture risk was significantly higher for larger aneurysms compared with smaller aneurysms (P<0.05)., Conclusion: More women suffered from MirAn than nMirAn or SingAn. The most common MirAn sites were the internal carotid-posterior communicating arteries. Our results suggest that MirAn was not associated with age, smoking, hypertension, or diabetes.

Introduction: Intracranial arteriovenous malformations (AVMs) are associated with high morbidity and mortality. Modern microsurgery has improved the results of surgical treatment of AVMs; however, the treatment of AVMs, particularly eloquently located AVMs, still carries a high risk. Functional MRI (fMRI) has been reported to be used for the preoperative evaluation of AVMs in small case series. The purpose is to identify the utility and efficacy of fMRI-guided microsurgery of AVMs in a large randomised controlled trial., Methods and Analysis: The study is a prospective, randomised controlled clinical trial. This study will enrol a total of 600 eligible patients. These eligible patients will be randomised to the standard microsurgery group and the fMRI-guided microsurgery group in a 1:1 ratio. Patient baseline characteristics and AVM architecture and characteristics will be described. In the fMRI-guided group, fMRI mapping of an eloquent cortex in all AVMs will be identified. Surgical complications and outcomes at pretreatment, post-treatment, at discharge and at 1-month, 3-month and 6-month follow-up intervals will be analysed using the modified Rankin Scale (mRS). This trial will determine whether fMRI-guided microsurgery could improve outcomes in patients with AVMs and also identify the safety and efficacy of fMRI-guided microsurgery., Ethics and Dissemination: The study protocol and written informed consent were reviewed and approved by the Institutional Review Board of Beijing Tiantan Hospital Affiliated to Capital Medical University (ky2012-016-02). Study findings will be disseminated in the printed media., Trial Registration Number: ClinicalTrials.gov NCT01758211., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Protein kinase B (PKB/Akt), which is phosphorylated and activated by upstream activators, exerts critical neuroprotective effects by phosphorylating downstream targets after traumatic brain injury (TBI). Studies on the regulation of Akt will be crucial for our understanding of neuronal survival. The goal of this study is to investigate the effects of carboxyl-terminal modulator protein (CTMP) on phosphorylation of Akt and neurological function in a mouse model of TBI., Methods: Traumatic brain injury in mice was performed by a controlled cortical impact device. The expression of Akt, phospho-Akt, and CTMP was examined in the injured cortices by immunohistochemistry and Western blot analysis. To determine the effects of CTMP, small interfering RNAs (siRNAs) directed against CTMP were injected in mice with TBI, and the expression of phosphorylated Akt and neurological function were evaluated., Results: Phospho-Akt significantly increased at 4 hours post-TBI in the nucleus (P < 0.01) and remained at high levels until 72 hours after TBI, as shown by Western blot analysis. In the cytosol, the expression of phospho-Akt reached its peak at 4 hours post-TBI, but decreased markedly at 24 hours and maintained below pre-TBI levels until 72 hours post-TBI. Interestingly, the expression of CTMP significantly increased 4 hours after TBI (P < 0.01) and sustained those levels until 72 hours without dramatic changes. Treatment with CTMP siRNA effectively augmented the phosphorylation of Akt and significantly improved the neurological functional recovery up to 28 days post-TBI., Conclusion: We conclude that Akt is phosphorylated and translocated to nucleus after TBI to exert neuroprotective effects. However, CTMP is simultaneously triggered to inhibit the phosphorylation of Akt. Inhibition of CTMP by siRNA improves the recovery of neurological functions after TBI.

Objective: To explore new treatment modalities for complex intracranial aneurysms., Methods: Under general anesthesia, intracranial aneurysm parent artery remodeling surgery was performed along with repeated immediate intraoperative cerebral angiogram to verify the effect of revascularization and therefore adjust the operation plan accordingly., Results: Aneurysm was successfully clipped without injuries of vascular branches. Prognosis was excellent., Conclusion: Complex hybrid surgery is an ideal option for parent artery remodeling of complicated intracranial aneurysms.

In this study, we extracted total RNA from 15 intracranial aneurysms and 17 superficial temporal artery samples, then performed genome-wide expression profiling using the Affymetrix U133 Plus 2.0 GeneChip. Genes that were differentially expressed between intracranial aneurysms and arterial samples were identified using significance analysis for microarrays, and the expression patterns of three randomly-selected genes were verified by real-time polymerase chain reaction analysis. We identified 3 736 differentially-expressed genes out of the 47,000 assayed transcripts. A total of 179 genes showed a >10-fold change in expression between the aneurysms and the arterial samples. Genes involved in the proliferation, migration, and apoptosis of vascular muscle cells, atherosclerosis, extracellular matrix disruption, and inflammatory reactions were associated with the formation of intracranial aneurysms. There were no significant differences in gene expression profile between unruptured and ruptured aneurysms.

Aim: To test the hypothesis that lymphocyte infiltration in brain arteriovenous malformation (bAVM) is not associated with iron deposition (indicator of microhemorrhage)., Methods: Sections of unruptured, previously untreated bAVM specimens (n=19) were stained immunohistochemically for T-lymphocytes (CD3 + ), B-lymphocytes (CD20 + ), plasma cells (CD138 + ) and macrophages (CD68 + ). Iron deposition was assessed by hematoxylin and eosin and Prussian blue stains. Superficial temporal arteries (STA) were used as control., Results: Both T lymphocytes and macrophages were present in unruptured, previously untreated bAVM specimens, whereas few B cells and plasma cells were detected. Iron deposition was detected in 8 specimens (42%; 95% confidence interval =20-67%). The samples with iron deposition tended to have more macrophages than those without (666±313 vs 478±174 cells/mm 2 ; P=0.11). T-cells were clustered on the luminal side of the endothelial surface, on the vessel-wall, and in the perivascular regions. There was no correlation between T lymphocyte load and iron deposition (P=0.88). No macrophages and lymphocytes were detected in STA controls., Conclusions: T-lymphocytes were present in bAVM specimens. Unlike macrophages, the load and location of T-lymphocytes were not associated with iron deposition, suggesting the possibility of an independent cell-mediated immunological mechanism in bAVM pathogenesis.

Objective: To investigate the long term outcomes after conservative and surgical treatment for haemorrhagic moyamoya disease., Methods: 97 consecutive patients with haemorrhagic moyamoya disease from 1997 to 2009 were enrolled in this study (mean age 31±10 years; range 5-56 years). We reviewed the clinical charts and radiographs of patients at the first bleeding episode. Follow-up was obtained prospectively by questionnaires and radiographic examinations. Outcomes were compared based on initial treatment (conservative vs surgical)., Results: After a median follow-up of 7.1 years, 21 of the 97 (21.7%) patients developed a second episode of bleeding, and six patients (6.2%) died of intracranial rebleeding. The median interval from initial episode to subsequent rebleeding was 9.1 years (0.1-23.2 years). 17 of 43 (37.1%) conservatively treated patients and four of 54 (7.4%) surgically treated patients experienced a rebleeding event (OR 8.1; 95% CI 2.4 to 26.8; p<0.001). There was a difference in the Kaplan-Meier curve of rebleeding between the two groups (Breslow test p=0.047; log rank test p=0.05). The rebleeding ratio in patients who underwent direct bypass was lower than that in patients treated with indirect bypass alone (0% vs 28.5%, 95% CI 1.0 to 1.9; p=0.002). No significant correlation was found between rebleeding and the patient's age, sex, location of haemorrhage, hypertension status or presence of cerebral aneurysm (p>0.05)., Conclusions: There is a high risk of rebleeding after the first haemorrhagic episode in Chinese patients with haemorrhagic moyamoya disease. Revascularisation surgery can improve regional blood flow and have greater efficacy at preventing rebleeding than conservative treatment.

The utility of PSVue 794 (PS794), a near-infrared fluorescent dye conjugated to a bis[zinc (II)-dipicolylamine] (Zn-DPA) targeting moiety, in imaging brain infarct was assessed in a rat middle cerebral artery occlusion-reperfusion model. Following reperfusion, 1 mM PS794 solution was administered intravenously via a tail vein. Fluorescence images were captured between 6 to 72 hours postinjection using a LI-COR Biosciences Pearl Imaging System. Strong fluorescence signals, which may represent the infarct core, were detected in the right hemisphere, ipsilateral to the injured site, and weaker signals in areas surrounding the core. In ischemia-reperfusion rats injected with a control dye not linked to a targeting agent, fluorescence was distributed diffusely throughout the brain. To address the issue of whether Zn-DPA targets apoptotic/necrotic cells, HT22 mouse hippocampal neurons were cultured in either Dulbecco's Modified Eagle's Medium, serum-deprived medium, Hank's Balanced Salt Solution, or L-glutamate (10 mM)-containing medium for up to 33 hours. Cells were then double-labeled with PSVue 480 (Zn-DPA conjugated to fluorescein isothiocyanate) and propidium iodide, which labels necrotic cells. Microscopic examination revealed that PS480 targeted apoptotic and necrotic cells. The result indicates that PS794 is applicable to in vivo imaging of brain infarct and that Zn-DPA selectively targets apoptotic/necrotic cells.

Unlabelled: Acupuncture is a form of Eastern medicine that has been practiced for centuries. Despite its long history and worldwide application, the biological mechanisms of acupuncture in relieving pain have been poorly defined. Recent studies in mice, however, demonstrate that acupuncture triggers increases in interstitial adenosine, which reduces the severity of chronic pain through adenosine A1 receptors, suggesting that adenosine-mediated antinociception contributes to the clinical benefits of acupuncture. We asked here whether acupuncture in human subjects is also linked to a local increase in interstitial adenosine concentration. We collected microdialysis samples of interstitial fluid before, during, and after delivering 30 minutes of conventional acupuncture in the Zusanli point in human subjects. The interstitial adenosine concentration increased significantly during acupuncture and remained elevated for 30 minutes after the acupuncture. Acupuncture-mediated adenosine release was not observed if acupuncture was not delivered in the Zusanli point or if the acupuncture needle was inserted, but not rotated. This study strengthens the role of adenosine in acupuncture-mediated antinociception by directly providing such evidence in humans., Perspective: This article presents further evidence of the role of adenosine in acupuncture-mediated antinociception by demonstrating that local adenosine concentrations increase in the acupoint in human subjects receiving traditional acupuncture., (Copyright © 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.)

In this study, we determined the expression levels of matrix metalloproteinase-2 and -9 and matrix metalloproteinase tissue inhibitor-1 and -2 in brain tissues and blood plasma of patients undergoing surgery for cerebellar arteriovenous malformations or primary epilepsy (control group). Immunohistochemistry and enzyme-linked immunosorbent assay revealed that the expression of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with cerebellar arteriovenous malformations than in patients with primary epilepsy. The ratio of matrix metalloproteinase-9 to matrix metalloproteinase tissue inhibitor-1 was significantly higher in patients with hemorrhagic cerebellar arteriovenous malformations compared with those with non-hemorrhagic malformations. Matrix metalloproteinase-2 and matrix metalloproteinase tissue inhibitor-2 levels were not significantly changed. These findings indicate that an imbalance of matrix metalloproteinase-9 and matrix metalloproteinase tissue inhibitor-1, resulting in a relative overabundance of matrix metalloproteinase-9, might be the underlying mechanism of hemorrhage of cerebellar arteriovenous malformations.

Objective: Apoptotic cell death is an important factor influencing the prognosis after traumatic brain injury (TBI). Akt/GSK-3beta/beta-catenin signaling plays a critical role in the apoptosis of neurons in several models of neurodegeneration. The goal of this study was to determine if the mechanism of cell survival mediated by the Akt/GSK-3beta/beta-catenin pathway is involved in a rat model of TBI., Methods: TBI was performed by a controlled cortical impact device. Expression of Akt, phospho-Akt, GSK-3beta, phospho-GSK-3beta, beta-catenin, phospho-beta-catenin were examined by immunohistochemistry and Western blot analysis. Double immunofluorenscent staining was used to observe the neuronal expression of the aforementioned subtrates. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) staining was performed to identify apoptosis., Results: Western blot analysis showed that phospho-Akt significantly increased at 4 hours post-TBI, but decreased after 72 hours post-TBI. Phospho-GSK-3beta - phosphorylated by phospho-Akt - slightly increased at 4 hours post-TBI and peaked at 72 hours post-TBI. These changes in Phospho-GSK-3beta expression were accompanied by a marked increase in expression of phospho-beta-catenin at 4 hours post-TBI which was sustained until 7 days post-TBI. Double staining of phospho-Akt and NeuN revealed the colocalization of phospho-Akt positive cells and neuronal cells. In addition, double staining of phospho-Akt and TUNEL showed no colocalization of phospho-Akt cells and TUNEL-positive cells., Conclusion: Phosphorylation of Akt (Ser473) and GSK3beta (Ser9) was accelerated in the injured cortex, and involved in the neuronal survival after TBI. Moreover, neuroprotection of beta-catenin against ischemia was partly mediated by enhanced and persistent activation of the Akt/GSK3beta signaling pathway.

Objective: To observe the hemodynamic changes of the superficial temporal artery (STA) by color Doppler and the correlation between the results of angiography and the hemodynamic changes of the STA after superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery for moyamoya disease., Methods: This study included 26 cases of moyamoya disease; standard STA-MCA bypass surgery were performed in all patients. GE-LOGIQ9 color ultrasound with 7L transducer was used to monitor STA hemodynamic changes, including peak systolic velocity (PSV), end-diastolic velocity (EDV), mean flow velocity (Vm), pulse index (PI), and resistance index (RI), preoperatively and 1 week and 3 months after surgery in 10 cases. In 22 cases, color Doppler of STA and digital subtraction angiography of the external carotid artery (ECA), internal carotid artery (ICA), common carotid artery (CCA), and vertebral artery (VA) were performed preoperatively and 1 week after surgery. Based on the patency of STA-MCA on angiography, the patients were divided into two groups: 11 patients were in the patent group, and 11 patients were in the nonpatent group. Statistical significance was evaluated using analysis of variance of random block design and paired samples t test. SPSS software version 11.5 was used., Results: In the 10 cases, there was no significant difference among the three imaging series in PSV. Compared with the preoperative values, the values of EDV and Vm 1 week and 3 months after surgery were significantly higher (P < 0.05). The difference was not significant, however, between 1 week and 3 months after surgery. The PI and RI at 1 week and 3 months after surgery were significantly lower than the preoperative values (P < 0.05); there was no significant difference between 1 week and 3 months after surgery. Among the 22 cases, the values of PSV, EDV, and Vm increased significantly (P < 0.05) and the values of PI and RI decreased significantly(P < 0.01) after surgery in the patent group. In the nonpatent group, the values of PSV and PI decreased significantly after surgery (P < 0.05). EDV, Vm, and RI had no significant changes after surgery., Conclusions: Higher blood flow can develop in anastomosed STA after STA-MCA bypass surgery. The hemodynamic changes of STA after surgery mainly occurred at an early period after operation with little change at 3-month follow-up examination. The increase of blood flow in STA may be due to the low resistance of the intracranial vascular bed. Postoperative Doppler examination of the STA may predict angiographic results of the anastomosis in the early postoperative period. Continuous observation is necessary to identify an accurate correlation between quantitative alteration of the Doppler parameters and angiographic results., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The treatment of giant arteriovenous malformations (AVMs) remains a challenge in the neurosurgical field. Microsurgery is one of the most effective ways for eliminating giant cerebral AVMs., Objective: To review surgical outcomes in treating the disease, and form conclusions regarding the indications for and outcomes of surgical treatment in giant intracranial AVMs., Methods: We studied 40 consecutive cases of giant AVMs treated in Beijing Tiantan Hospital between 2000 and 2008. The radiologic and clinical features were analyzed. The Spetzler-Martin grading system was used to classify the patients. All patients were surgically treated, and the final outcomes of the patients were gathered for analysis., Results: The major presenting symptoms were seizures, headaches, hemorrhage, and neurological deficits. The mean AVM diameter was 6.3 cm. According to the Spetzler-Martin grading system, 5 patients had grade III lesions, 21 had grade IV lesions, and 14 had grade V lesions. Out of the total 40 patients, 31 (77.5%) demonstrated excellent or good outcome. Complications included hemiparalysis, aphasia, hemianopia, cranial nerve dysfunction, and seizures. After follow-up, 27 of 30 (90%) surviving patients presented normal function or minimal symptoms., Conclusion: Presurgical evaluation of every candidate and treatment choice is the determining factor in therapy for giant AVMs. For giant cerebral AVMs located superficially or not involving critical components, a good outcome can be expected through surgical resection. The obliteration and recurrence rates were satisfying, and the complication rate was acceptable.

The primary aim of this study is to assess the value of intraoperative near-infrared indocyanine green videoangiography (ICGA) during intracranial aneurysm surgery. Altogether, 129 patients harboring 152 intracranial aneurysms were recruited in this study between March 2007 and December 2008 and the clinical data were retrospectively analyzed. Intraoperative ICGA was performed to examine the completeness of the aneurysm clipping and the patency of the parent arteries in all cases. The intraoperative findings were compared with that of postoperative digital subtraction angiography (DSA). On all of the patients, 276 successful ICGA investigations were performed intraoperatively. The image quality and resolution were excellent, allowing real-time assessment of the cerebral circulation. Indocyanine green (ICG) angiographic results could be divided into arterial, capillary, and venous phases, comparable to those observed with postoperative DSA. In all cases, the postoperative angiographic results corresponded to the intraoperative ICGA findings. In three cases, the information provided by intraoperative ICG angiography significantly changed the surgical procedure. Intraoperative ICG videoangiography may be a useful tool in real-time evaluation of the aneurysm clipping. Its simplicity and easy reproducibility all suggest it to be carried out as a routine procedure during aneurysm surgery.

The application of nanomaterial in cancer treatment is promising and intriguing. Anti-tumor immunotherapy has the potential to significantly improve the prognosis of cancer treatment, though the efficacy of immunotherapy generally needs further improvement. One way to improve the efficacy is using immune adjuvants, but the adjuvants for anticancer immunotherapy have to be more potent than for prophylactic vaccines. Here, we report that compared to conventional alum adjuvant, aluminum oxide nanoparticles (nano-alum) may further enhance the anticancer effects of an immunotherapy that employs tumor cell vaccine (TCV). The average tumor size tends to be lower in animals that receive the combinational treatment of nano-alum and TCV. The anticancer cytotoxicity by the lymphocytes was also significantly higher in the treatment group that received both TCV and nano-alum. These results suggest that nano-alum may potentially serve as a potent immune adjuvant and have prospective applications in anticancer immunotherapy.

Objectives: The objective was to describe the clinical features of intracranial aneurysm in children and evaluate the efficacy and safety of different treatment approaches for children with intracranial aneurysms., Materials and Methods: Clinical data of 13 child patients with intracranial aneurysms that were diagnosed and treated in our hospital in the past 16 years were reviewed. Long-term follow-up data were also collected and reported., Results: Direct surgical treatment was performed on eight out of all 13 patients; among them, seven achieved good recovery and one died. The remaining five patients were treated with Guglielmi detachable coils (GDC). The aneurysm was successfully sealed off in one case and achieved good postoperative recovery. Residual aneurysm was detected in two cases; a second resection surgery was performed on one patient who died after the operation and on another with neck occlusion who recovered well. Two cases experienced aneurysm recanalization after interventional therapy; among them, one was treated with a second embolotherapy but had recanalization once again and was finally cured by aneurysm resection surgery., Conclusion: Aneurysmal surgery is proved to be a safe and effective treatment for children with intracranial aneurysm. Although requiring a long-term follow-up period to determine the clinical outcome, GDC is also shown to be safe for a child having acute bleeding. Once a residual aneurysm or recanalization occurs, microsurgery is recommended.

The modification on the titanium implant surface is an effective method to improve the biocompatibility of titanium. This article describes efforts to improve implant biocompatibility by applying titania and hydroxyapatite to form a three-layer coating on the titanium surface. This three-layer coating is made up of HA as the top layer (formed by hydrothermal treatment), porous TiO2 as the middle layer (formed by micro-arc oxidation) and a dense TiO2 film as the inner layer (formed by preanodic oxidation). The physicochemical characteristics, cell behavior and in vivo studies were assessed. The physicochemical characteristics were investigated using scanning electron micoscopy observation, fibronectin and laminin adsorption, corrosion test and X-ray diffraction analysis. Cell behavior included morphology observation with scanning electron microscopy (SEM), number count with methylthiazol tetrazolium (MTT) assay and Alkaline phosphatase (ALP, a representative enzyme of osteoblastic differentiation) activity of osteoblast-like MC3T3-E1 cells. In study in vivo the specimens were embedded in skull wound for repair. By the analysis of experiments, the titanium coated with this three-layer coating has been proved to have excellent corrosion resistance and good biocompatibility, which can promote cell proliferation and bone formation. So this modified titanium is an improved alternative to untreated titanium for bone repair applications., ((c) 2007 Wiley Periodicals, Inc. J Biomed Mater Res 2007.)

The objective of this study was to retrospectively investigate the surgical indications, operation methods, and postoperative results of patients with cavernous malformations (CMs) and the use of neuronavigation. Seventy patients with CMs were operated on in our hospital. The initial symptoms were hemorrhage in 31 cases, seizures in 29 cases, focal neurological deficit in 4 cases, and headache in 5 cases. Only one asymptomatic case was incidentally identified by radiological examination. The size of CMs ranged from 5 to 50 mm (mean: 21 mm). The CMs in 39 patients were located within the white matter of the hemispheres, 11 within the basal ganglia or thalamus, 5 within the cerebellum, and 6 in multiple locations. Prior to the operation, five fiducial markers were placed on the scalp and magnetic resonance imaging (MRI) was performed. Data were transferred to the neuronavigation workstation, a profile of tumors was drawn up, and a three-dimensional reconstruction was completed. The foci were separated and resected under a microscope through a sulci and fissures approach. All the lesions were resected totally. No residual foci were found by postoperative computed tomography (CT)/MRI examination, and there was no operative death. The disability rate was 8.6%; four patients had a new transitory neurological deficit within 1 month after the operation, and one patient with thalamic CMs developed facial paralysis. All patients, however, recovered in 6 months. Twenty-four patients with preoperative epilepsy were followed up for 6-24 months (mean: 19.4 months). After the operation, seizures disappeared in 19 patients and symptoms improved in 5. CMs can be determined in patients even if patients are asymptomatic. Surgical treatment should be considered if bleeding occurs. An operation with the guidance of neuronavigation is safe and can decrease the occurrence of disability following the procedure.

This study was designed to compare the approaches and efficacies of two different ways of neurosurgical management for spontaneous putaminal hemorrhage (SPH): computed tomographic-guided aspiration (CTGA) and the key-hole approach (KHA). The indications of the two approaches are also explored. From September 2001 to 2003, a total of 1077 cases of SPH distributed in 135 hospitals all over the mainland of China were included for analysis. All cases had three-month follow-up data. The study was designed in a single-blinded manner to compare the efficacies of the different approaches. There were 563 cases in the CTGA group, 165 in the KHA group, and 217 cases in the conventional open craniotomy (COC) group. In the CTGA and KHA groups, the mortalities at one month after operation (M1m) were 17.9% and 18.3%, respectively, while the mortalities at three months after operation (M3m) were 19.4% and 19.4%, respectively (P>0.05). The postoperative complications due to CTGA (23.7%) were not significantly different from those due to KHA (25.7%) (P = 0.420). The M3m of patients with Glasgow coma scale (GCS) [Symbol: see text]8 was 3.45 and 4.0 times as much as those with GCS>8, respectively. The M3m of patients with complications was 3.92 times as much as those without complications. The M3m of patients with hemorrhage volume [Symbol: see text]70 mL was 2.67 times as much as those <70 mL. The CTGA is not better than KHA in the treatment of SPH in terms of a more favorable outcome or less mortality and morbidity, but CTGA could be the first choice for those with bleeding volumes ≤50mL, while KHA is the first choice for those with bleeding volumes >50 mL.

The utility of a neuronavigation system in the transsphenoidal surgery of pituitary macroadenoma was evaluated, and improvement of the surgical outcome is discussed. From 1997 to 2003, a total of 63 patients (male:female=41:22, mean age 58.3 years) with pituitary macroadenoma were treated surgically via transsphenoidal approach using a neuronavigation system in Beijing Tiantan Hospital. Image data for computed tomography or magnetic resonance were obtained and analyzed by the navigation system to make a three-dmensional reconstruction. During the operation, the tumor and its surrounding structures of the sellar region could be located accurately at any time. Among these cases, the tumors were removed totally in 26 cases (41.3%), subtotally in 36 cases (57.1%) and partially in one case (1.6%). Postoperative neurological complications occurred in 15 cases (23.8%). One patient died, the operative mortality was 1.6%. During the operation, the accuracy of the neuronavigation system was 2.3+/-1.1 mm. The neuronavigation system is quite helpful for transsphenoidal surgery of pituitary macroadenoma. Its accuracy of location is very useful and important in determining anatomical structure and protecting normal tissues and vessels. Moreover, fluoroscopy was not required during the surgery.

This paper describes efforts to improve implant biocompatibility and durability by applying a hybrid technique using composite oxidation. Pure titanium was used as the substrate material. A porous oxide film as the outer layer was produced by micro-arc oxidation and a dense oxide film as the inner layer was produced by pre-anodic oxidation. In this study, physicochemical characteristics, corrosion test, cell attachment behavior, and in vivo studies were used to compare this gradient layer with untreated titanium. The results revealed that the gradient layer was composed of two layers of oxide films which were made up of rutile and anatase and the surface was porous with calcium and phosphor. The corrosion resistance of the gradient layer was improved remarkably, which was about three times the values for titanium and two times the value for the dense layer. The cell-material interaction study indicated that L929 cells seeded and cultured on the gradient layer appeared to attach well and the rate of proliferation was the greatest. The study in vivo showed that the gradient layer had good biocompatibility. This gradient layer provides a material with high corrosion resistance, bioactivity, and biological properties suitable for tissue engineering applications.

Objective: To evaluate the management of carotid-ophthalmic segment aneurysms (COA) with modern microneurosurgical techniques and instruments., Method: Sixty patients with COA undergoing microsurgical clipping between March 1994 and June 2002 in the Department of Neurosurgery, Tiantan Hospital, Beijing, were analyzed retrospectively. Neuroimaging included digital subtraction angiography (DSA), MRI, CT, three-dimensional CT angiography and three-dimensional DSA. From 1998, intraoperative Doppler ultrasound monitoring and endoscope-assisted techniques were used., Result: All aneurysms were completely obliterated without either recurrence or death. The morbidity rate of surgery prior to 1998 was 21.7%, which decreased to 13.7% after 1998 (mean 18.3% for the whole study period)., Conclusion: Preoperative planning based on neuroimaging is very valuable. Advances in neuroimaging, endoscope-assisted techniques and intraoperative Doppler ultrasound monitoring are useful to decrease postoperative complications. Microneurosurgical techniques are optimal for the management of COA with ever lessening morbidity.

Background: Cerebral arteriovenous malformation (AVM) is a common vascular disease in neurosurgery, and the indication for alternative treatments remains controversial. In a review of a series of 2086 patients with AVMs, the clinical characteristics and surgical results were assessed., Methods: Collected data of 2086 consecutive patients with AVMs from January 1956 to October 2001 were analyzed. All patients were divided into 2 groups: traditional surgery group (from 1956 to 1991) and microsurgery group (from 1992 to 2001). The variables assessed for clinical characteristics in our study included age (at presentation), sex, Spetzler-Martin grade, and first presentations. Surgical complications were assessed between different surgery groups by chi(2) test., Results: Cerebral AVMs are more commonly diagnosed at age of 20 to 40 years, which comprises almost one half of the whole population. The size of the AVMs ranged from 1 to 9 cm. There were 77 cases of giant AVMs in this series that were treated by a combination of surgical resection and intraoperative embolization. Hemorrhage (43.4%), headache (24.9%), and seizure (17.3%) were the first 3 common presentations. Regarding Spetzler-Martin grading system, the percentage of grade 3 to 5 patients increased, whereas that of grade 1 patients decreased in the microsurgery group (P = .00). However, compared with the traditional surgery group, the incidence of main surgical complications (death, hemiparalysis, cranial nerve dysfunction, and gastrointestinal hemorrhage) decreased significantly in the microsurgery group (P = .00). Although the incidence of main surgical complications had no statistical difference between early (from 1992 to 1996) and late microsurgery subgroup (from 1997 to 2001) (P = .796), the incidence really decreased with increase of higher-grading patients (grade 3-5) in the late microsurgery group (P = .00)., Conclusions: Cerebral AVM is one of the important reasons for spontaneous intracranial hemorrhage in patients younger than 40. Spetzler-Martin grading system is helpful to predict the surgical risk. Microsurgical technique has made surgical treatment safer and become the best choice for patients with cerebral AVM.

Objective: To study the morbidity and mortality of patients with aneurysms of the posterior circulation (basilar-vertebral system) and investigate the natural history of these aneurysms without surgical intervention., Methods: Of 1232 patients with intracranial aneurysms admitted to Tiantan Hospital from January 1990 to October 2001, 153 (12.4%) had aneurysms of the posterior circulation. Their clinical and angiographic data were reviewed retrospectively. Additionally, to June 2002, 38 of the cases managed without surgery have been followed by telephone and correspondence. For these patients, the annual aneurysm rupture rate was estimated in "person-years"., Results: Patients were aged 4-69 years (mean 40.8). The peak incidence was in the 5th decade. There were 88 males and 65 females. One hundred and two patients (66.7%) were treated surgically, and of these, 60 (58.8%) had an excellent outcome, 10 (9.8%) a good outcome, 29 (28.4%) a fair outcome and 3 (2.9%) died. The other 51 (33.3%) patients were treated conservatively for various reasons. Of these, 13 died of ruptured aneurysm in hospital. Ten of these patients had had a previous subarachnoid haemorrhage and 3 had not. The other 38 surviving, conservatively managed patients were followed for 5-95 months (mean 23). Of them, 3 (17.6%) died of aneurysmal rupture, giving an annual rupture rate of 9.2%, or 3/32.47 patient years., Conclusions: To prevent death and disability due to aneurysmal rupture, posterior circulation aneurysms should be treated aggressively.

Background: The APOE-E4 allele has been identified as a risk factor for Alzheimer's disease and unfavorable outcomes after brain injuries. The purpose of this study was to confirm that APOE allele polymorphism also represents a risk factor for unfavorable outcomes following aneurysmal subarachnoid hemorrhage (SAH)., Methods: A total of 104 patients with aneurysmal SAH were studied. Computed tomography (CT) scan findings of SAH were assessed by Fisher's grade and clinical neurologic assessment was performed using the Hunt and Hess (H&H)grading system. Serum lipids were also analyzed. Outcomes at 3 months after SAH were determined using the Glasgow Outcome Scale., Results: The distributions of APOE genotypes and alleles of patients were matched with those of control subjects. That 5 of 18 patients with APOE-E4 allele (28%) had an unfavorable outcome was significantly different from those without APOE-E4 (8%, chi2, p = 0.032; OR = 4.34, 95% CI 1.20-15.75). However, the presence or absence of E2 or E3 alleles had no significant difference. The relative hazard of APOE-E4 for unfavorable outcome exited after adjustment for clinical assessment (OR = 6.95, 95% CI 1.21-39.75). Total serum cholesterol, low-density lipoprotein and apolipoprotein B were elevated in patients with unfavorable rather than favorable outcomes., Conclusion: Our findings confirmed that the patients with APOE-E4 allele were predisposed to unfavorable outcomes after aneurysmal SAH even though an association between APOE and incidence of the SAH may not exist. The effect of APOE on neurobiology and lipoprotein metabolism seems to partially explain the difference in outcomes and deserves further study.

A CENTURY IS quite a short time in the history of humankind, but there have been significant happenings in the field of neurosurgery in China during the past century. We review the history of the founding and development of neurosurgery in China. We record these events faithfully, and we also dedicate this article to those pioneers, including Song-Tao Guan, Yi-Cheng Zhao, and others, who devoted their lives to neurosurgery in China.