Yamei Tang

Clipping Versus Coiling for Ruptured Intracranial Aneurysms A Systematic Review and Meta-Analysis

Background and Purpose— Endovascular treatment has increasingly been used for aneurismal subarachnoid aneurismal hemorrhage. The aim of this analysis is to assess the current evidence regarding safety and efficiency of clipping compared with coiling. Methods— We conducted a meta-analysis of studies that compared clipping with coiling between January 1999 and July 2012. Comparison of binary outcomes between treatment groups was described using odds ratios (OR; clip versus coil). Results— Four randomized controlled trials and 23 observational studies were included. Randomized controlled trials showed that coiling reduced the 1-year unfavorable outcome rate (OR, 1.48; 95% confidence interval [CI], 1.24–1.76). However, there was no statistical deference in nonrandomized controlled trials (OR, 1.11; 95% CI, 0.96–1.28). Subgroup analysis revealed coiling yielded better outcomes for patients with good preoperative grade (OR, 1.51; 95% CI, 1.24–1.84) than for poor preoperative patients (OR, 0.88; 95% CI 0.56–1.38). Additionally, the incidence of rebleeding is higher after coiling (OR, 0.43; 95% CI, 0.28–0.66), corresponding to a better complete occlusion rate of clipping (OR, 2.43; 95% CI, 1.88–3.13). The 1-year mortality showed no significant difference (OR, 1.07; 95% CI, 0.88–1.30). Vasospasm was more common after clipping (OR, 1.43; 95% CI, 1.07–1.91), whereas the ischemic infarct (OR, 0.74; 95% CI, 0.52–1.06), shunt-dependent hydrocephalus (OR, 0.84; 95% CI, 0.66–1.07), and procedural complication rates (OR, 1.19; 95% CI, 0.67–2.11) did not differ significantly between techniques. Conclusions— Coiling yields a better clinical outcome, the benefit being greater in those with a good preoperative grade than those with a poor preoperative grade. However, coiling leads to a greater risk of rebleeding. Well-designed randomized trials with special considerations to the aspect are needed.

Psychological disorders, cognitive dysfunction and quality of life in nasopharyngeal carcinoma patients with radiation-induced brain injury.

Purpose To evaluate factors affecting psychology, cognitive function and quality of life (QOL) of nasopharyngeal carcinoma (NPC) patients with radiation-induced brain injury (RI). Methods and Materials 46 recurrence-free NPC patients with RI and 46 matched control patients without RI were recruited in our study. Subjective and objective symptoms of RI were evaluated with the LENT/SOMA systems. Psychological assessment was measured with Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS). Montreal Cognitive Assessment (MoCA) was carried out in these patients for assessing their cognitive function. QOL was evaluated by means of WHOQOL BREF. Results Of the patients with RI, 39(84.8%) had depression and 40(87.0%) had anxiety. The patients with RI got higher scores both in SDS and SAS than those without RI (SDS, 63.48±8.11vs. 58.67±7.52, p = 0.008; SAS, 67.36±10.41vs. 60.34±9.76, p = 0.005). Score in MoCA of patients with RI was significantly lower than that of patients without RI (21.32±2.45vs. 25.98±1.73, p<0.001). SAS was positive correlated with post-radiotherapy interval. Both SAS and SDS had a significantly positive correlation with the rank of SOMA, while MoCA had a significantly negative correlation with SOMA. Chemotherapy was a risk factor for cognitive dysfunction. In addition, patients with RI got significantly lower scores in physical health (16.50±11.05 vs. 35.02±10.43, p<0.001), psychological health (17.70±10.33 vs. 39.48±12.00, p<0.001) and social relationship (48.00±18.65 vs. 67.15±19.70, p<0.001) compared with those in patients without RI. Multiple linear regression analysis revealed that anxiety and cognitive impairment were significant predictors of global QOL. Conclusions NPC patients with RI exhibit negative emotions, impaired cognitive function and QOL. The severity of clinical symptoms of RI plays an important role in both emotions and cognitive function. Anxiety and cognitive impairment are associated with decreased QOL.

Blockade of Kv1.3 channels ameliorates radiation-induced brain injury

BACKGROUND Tumors affecting the head, neck, and brain account for significant morbidity and mortality. The curative efficacy of radiotherapy for these tumors is well established, but radiation carries a significant risk of neurologic injury. So far, neuroprotective therapies for radiation-induced brain injury are still limited. In this study we demonstrate that Stichodactyla helianthus (ShK)-170, a specific inhibitor of the voltage-gated potassium (Kv)1.3 channel, protected mice from radiation-induced brain injury. METHODS Mice were treated with ShK-170 for 3 days immediately after brain irradiation. Radiation-induced brain injury was assessed by MRI scans and a Morris water maze. Pathophysiological change of the brain was measured by immunofluorescence. Gene and protein expressions of Kv1.3 and inflammatory factors were measured by quantitative real-time PCR, reverse transcription PCR, ELISA assay, and western blot analyses. Kv currents were recorded in the whole-cell configuration of the patch-clamp technique. RESULTS Radiation increased Kv1.3 mRNA and protein expression in microglia. Genetic silencing of Kv1.3 by specific short interference RNAs or pharmacological blockade with ShK-170 suppressed radiation-induced production of the proinflammatory factors interleukin-6, cyclooxygenase-2, and tumor necrosis factor-α by microglia. ShK-170 also inhibited neurotoxicity mediated by radiation-activated microglia and promoted neurogenesis by increasing the proliferation of neural progenitor cells. CONCLUSIONS The therapeutic effect of ShK-170 is mediated by suppression of microglial activation and microglia-mediated neurotoxicity and enhanced neurorestoration by promoting proliferation of neural progenitor cells.

Effects of early blood pressure lowering on early and long-term outcomes after acute stroke: an updated meta-analysis.

Background Hypertension is common after acute stroke onset. Previous studies showed controversial effects of early blood pressure (BP) lowering on stroke outcomes. The aim of this study is to assess the effects of early BP lowering on early and long-term outcomes after acute stroke. Methods A meta-analysis was conducted with prospective randomized controlled trials assessing the effects of early BP lowering on early and long-term outcomes after acute stroke compared with placebo. Literature searching was performed in the databases from inception to December 2013. New evidence from recent trials were included. Outcomes were analyzed as early (within 30 days) and long-term (from 3 to 12 months) endpoints using summary estimates of relative risks (RR) and their 95% confidence intervals (CI) with the fixed-effect model or random-effect model. Results Seventeen trials providing data from 13236 patients were included. Pooled results showed that early BP lowering after acute stroke onset was associated with more death within 30 days compared with placebo (RR: 1.34 and 95% CI: 1.02, 1.74, p = 0.03). However the results showed that early BP lowering had no evident effect on early neurological deterioration, early death within 7 days, long-term death, early and long-term dependency, early and long-term combination of death or dependency, long-term stroke recurrence, long-term myocardial infarction and long-term CVE. Conclusions The new results lend no support to early BP lowering after acute stroke. Early BP lowering may increase death within 30 days after acute stroke.

The protective effect of astaxanthin on fetal alcohol spectrum disorder in mice.

Astaxanthin is a strong antioxidant with the ability of reducing the markers of inflammation. To explore the protective effect of astaxanthin on maternal ethanol induced embryonic deficiency, and to investigate the underlying mechanisms, we detected the morphology, expression of neural marker genes, oxidative stress indexes, and inflammatory factors in mice model of fetal alcohol spectrum disorder with or without astaxanthin pretreatment. Our results showed that astaxanthin blocked maternal ethanol induced retardation of embryonic growth, and the down-regulation of neural marker genes, Otx1 and Sox2. Moreover, astaxanthin also reversed the increases of malondialdehyde (MDA), hydrogen peroxide (H2O2), and the decrease of glutathione peroxidase (GPx) in fetal alcohol spectrum disorder. In addition, maternal ethanol induced up-regulation of toll-like receptor 4 (TLR4), and the down-streaming myeloid differentiation factor 88 (MyD88), NF-κB, TNF-α, and IL-1β in embryos, and this was inhibited by astaxanthin pretreatment. These results demonstrated a protective effect of astaxanthin on fetal alcohol spectrum disorder, and suggested that oxidative stress and TLR4 signaling associated inflammatory reaction are involved in this process.

A Study of Radiation-Induced Cerebral Vascular Injury in Nasopharyngeal Carcinoma Patients with Radiation- Induced Temporal Lobe Necrosis

Purpose To investigate radiation-induced carotid and cerebral vascular injury and its relationship with radiation-induced temporal lobe necrosis in nasopharyngeal carcinoma (NPC) patients. Methods and Materials Fifty eight NPC patients with radiation-induced temporal lobe necrosis (TLN) were recruited in the study. Duplex ultrasonography was used to scan bilateral carotid arterials to evaluate the intima-media thickness (IMT) and occurrence of plaque formation. Flow velocities of bilateral middle cerebral arteries (MCAs), internal carotid arteries (ICAs) and basal artery (BA) were estimated through Transcranial Color Doppler (TCD). The results were compared with data from 33 patients who were free from radiation-induced temporal lobe necrosis after radiotherapy and 29 healthy individuals. Results Significant differences in IMT, occurrence of plaques of ICAs and flow velocities of both MCAs and ICAs were found between patients after radiotherapy and healthy individuals (p<0.05). IMT had positive correlation with post radiation interval (p = 0.049). Compared with results from patients without radiation-induced TLN, the mean IMT was significantly thicker in patients with TLN (p<0.001). Plaques were more common in patients with TLN than patients without TLN (p = 0.038). In addition, flow velocities of MCAs and ICAs in patients with TLN were much faster (p<0.001, p<0.001). Among patients with unilateral TLN, flow velocity of MCAs was significantly different between ipsilateral and contralateral sides to the lesion (p = 0.001). Conclusion Thickening of IMT, occurrence of plaque formation and hemodynamic abnormality are more common in patients after radiotherapy, especially in those with TLN, compared with healthy individuals.

Efficacy and Safety of Adding Clopidogrel to Aspirin on Stroke Prevention among High Vascular Risk Patients: A Meta-Analysis of Randomized Controlled Trials

Objectives Whether clopidogrel should be added to aspirin for stroke prevention remained controversial for the risk of hemorrhagic complications. This meta-analysis was aimed to assess the efficacy and safety of adding clopidogrel to aspirin on stroke prevention in high vascular risk patients, and to provide evidence for a suitable duration of dual antiplatelet therapy. Methods We searched PubMed, EMBase, OVID and Cochrane Central Register of Controlled Trials (up to June, 2013) for randomized controlled trials evaluating the efficacy and safety of clopidogrel plus aspirin versus aspirin alone in high vascular risk patients. Comparisons of stroke and hemorrhagic complications between treatment groups were expressed by the pooled Relative Risks (RRs) with 95% Confidence Intervals (CIs). Results Fifteen trials with a total of 97692 intention-to-treat participants were included with duration of follow-up ranging from 7 days to 3.6 years. Dual antiplatelet therapy reduced all stroke by 21% (RR: 0.79, 95% CI: 0.73–0.85) with no evidence of heterogeneity across the trials (P = 0.27, I 2 = 17%).The effects were consistent between short-term subgroup (≤1 month, RR: 0.76, 95% CI: 0.67–0.85) and long-term subgroup (≥3 months, RR: 0.81, 95% CI: 0.73–0.89). The risk of major bleeding was not significantly increased by dual antiplatelet therapy in short-term subgroup (RR: 1.11, 95% CI: 0.91–1.36), while significantly increased in long-term subgroup (RR: 1.52, 95% CI: 1.36–1.69). Long-term dual antiplatelet therapy substantially increased the risk of intracranial bleeding (RR: 1.76, 95% CI: 1.22–2.54). Conclusions This meta-analysis demonstrates that short-term combination of clopidogrel and aspirin is effective and safe for stroke prevention in high vascular risk patients. Long-term combination therapy substantially increases the risk of major bleeding and intracranial bleeding.

Rhubarb extract has a protective role against radiation-induced brain injury and neuronal cell apoptosis

Oxidative stress caused by ionizing radiation is involved in neuronal damage in a number of disorders, including trauma, stroke, Alzheimers disease and amyotrophic lateral sclerosis. Ionizing radiation can lead to the formation of free radicals, which cause neuronal apoptosis and have important roles in the development of some types of chronic brain disease. The present study evaluated the effects of varying concentrations (2, 5 and 10 µg/ml) of ethanolic rhubarb extract on the neuronal damage caused by irradiation in primary neuronal cultures obtained from the cortices of rat embryos aged 20 days. Brain damage was induced with a single dose of γ-irradiation that induced DNA fragmentation, increased lactate dehydrogenase release in neuronal cells and acted as a trigger for microglial cell proliferation. Treatment with rhubarb extract significantly decreased radiation-induced lactate dehydrogenase release and DNA fragmentation, which are important in the process of cell apoptosis. The rhubarb extract exhibited dose-dependent inhibition of lactate dehydrogenase release and neuronal cell apoptosis that were induced by the administration of ionizing radiation. The effect of a 10 µg/ml dose of rhubarb extract on the generation of reactive oxygen species (ROS) induced by radiation was also investigated. This dose led to significant inhibition of ROS generation. In conclusion, the present study showed a protective role of rhubarb extract against irradiation-induced apoptotic neuronal cell death and ROS generation.

Temporal Cerebral Microbleeds Are Associated With Radiation Necrosis and Cognitive Dysfunction in Patients Treated for Nasopharyngeal Carcinoma

PURPOSE Radiation therapy for patients with nasopharyngeal carcinoma (NPC) may be complicated with radiation-induced brain necrosis (RN), resulting in deteriorated cognitive function. However, the underlying mechanism of this phenomenon remains unclear. This study attempts to elucidate the association between cerebral microbleeds (CMBs) and radiation necrosis and cognitive dysfunction in NPC patients treated with radiation therapy. METHODS AND MATERIALS This cross-sectional study included 106 NPC patients who were exposed to radiation therapy (78 patients with RN and 28 without RN). Sixty-six patients without discernable intracranial pathology were included as the control group. CMBs were confirmed using susceptibility-weighted magnetic resonance imaging. Cognitive function was accessed using Montreal Cognitive Assessment. Patients with a total score below 26 were defined as cognitively dysfunction. RESULTS Seventy-seven patients (98.7%) in the RN group and 12 patients (42.9%) in the non-RN group had at least 1 CMB. In contrast, only 14 patients (21.2%) in the control group had CMBs. In patients with a history of radiation therapy, CMBs most commonly presented in temporal lobes (76.4%) followed by cerebellum (23.7%). Patients with RN had more temporal CMBs than those in the non-RN group (37.7 ± 51.9 vs 3.8 ± 12.6, respectively; P<.001). The number of temporal lobe CMBs was predictive for larger volume of brain necrosis (P<.001) in multivariate linear regression analysis. Although cognitive impairment was diagnosed in 55.1% of RN patients, only 7.1% of non-RN patients sustained cognitive impairment (P<.001). After adjusting for age, sex, education, period after radiation therapy, CMBs in other lobes, and RN volume, the number of temporal CMBs remained an independent risk factor for cognitive dysfunction (odds ratio [OR]: 1.03; 95% confidence interval [CI]: 1.01-1.04; P=.003). CONCLUSIONS CMBs is a common radiological manifestation in NPC patients with RN. The number of temporal CMBs is independently associated with increased likelihood of cognitive dysfunction in patients with RN.

Pathophysiological Responses in Rat and Mouse Models of Radiation-Induced Brain Injury

The brain is the major dose-limiting organ in patients undergoing radiotherapy for assorted conditions. Radiation-induced brain injury is common and mainly occurs in patients receiving radiotherapy for malignant head and neck tumors, arteriovenous malformations, or lung cancer-derived brain metastases. Nevertheless, the underlying mechanisms of radiation-induced brain injury are largely unknown. Although many treatment strategies are employed for affected individuals, the effects remain suboptimal. Accordingly, animal models are extremely important for elucidating pathogenic radiation-associated mechanisms and for developing more efficacious therapies. So far, models employing various animal species with different radiation dosages and fractions have been introduced to investigate the prevention, mechanisms, early detection, and management of radiation-induced brain injury. However, these models all have limitations, and none are widely accepted. This review summarizes the animal models currently set forth for studies of radiation-induced brain injury, especially rat and mouse, as well as radiation dosages, dose fractionation, and secondary pathophysiological responses.