Anti-vascular endothelial growth factor therapy for malignant glioma

Glioblastomas are among the most vascular tumors because they oversecrete vascular endothelial growth factor (VEGF), a potent stimulator of angiogenesis. Consequently, new drug regimens are being developed to target the VEGF signaling pathway in an attempt to halt tumor growth. Antibodies that bind VEGF, decoy molecules that sequester VEGF, and small molecule tyrosine kinase inhibitors that block receptor activation are being tested. Preliminary results with these agents have been promising, with prolonged progression-free survival reported. The antipermeability effects of anti-VEGF agents have important consequences for tumor imaging and for patient quality of life by decreasing corticosteroid dependence. However, because most patients eventually relapse, more work is needed to understand mechanisms of disease escape, including vascular cooption of native brain blood vessels.     

Cannabinoids in experimental stroke: a systematic review and meta-analysis

Cannabinoids (CBs) show promise as neuroprotectants with some agents already licensed in humans for other conditions. We systematically reviewed CBs in preclinical stroke to guide further experimental protocols. We selected controlled studies assessing acute administration of CBs for experimental stroke, identified through systematic searches. Data were extracted on lesion volume, outcome and quality, and analyzed using random effect models. Results are expressed as standardized mean difference (SMD) with 95% confidence intervals (CIs). In all, 144 experiments (34 publications) assessed CBs on infarct volume in 1,473 animals. Cannabinoids reduced infarct volume in transient (SMD −1.41 (95% CI −1.71), −1.11) P<0.00001) and permanent (−1.67 (−2.08, −1.27), P<0.00001) ischemia and in all subclasses: endocannabinoids (−1.72 (−2.62, −0.82), P=0.0002), CB₁/CB₂ ligands (−1.75 (−2.19, −1.31), P<0.00001), CB₂ ligands (−1.65 (−2.09, −1.22), P<0.00001), cannabidiol (−1.20 (−1.63, −0.77), P<0.00001), Δ⁹-tetrahydrocannabinol (−1.43 (−2.01, −0.86), P<0.00001), and HU-211 (−2.90 (−4.24, −1.56), P<0.0001). Early and late neuroscores significantly improved with CB use (−1.27 (−1.58, −0.95), P<0.00001; −1.63 (−2.64, −0.62), P<0.002 respectively) and there was no effect on survival. Statistical heterogeneity and publication bias was present, median study quality was 4 (range 1 to 6/8). Overall, CBs significantly reduced infarct volume and improve functional outcome in experimental stroke. Further studies in aged, female and larger animals, with other co-morbidities are required.     

Alcohol-related peripheral neuropathy: a systematic review and meta-analysis

Journal of Neurology - The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to...     

血管内皮生长因子Rs3025039基因多态性与脑卒中关联研究的Meta分析

目的系统评价血管内皮生长因子(vascular endothelial growth factor,VEGF)Rs3025039基因多态性与脑卒中关联性。方法检索Pub Med、EMbase、Wed of Science、The Cochrane Library、Elsevier、中国知网、中国生物医学文献数据库、万方数据库、维普数据库和中国科技论文在线中关于VEGF Rs3025039基因多态性与脑卒中关系研究,对纳入研究进行方法学质量评价,采用Rev Man 5.3软件进行Meta分析。结果共纳入11项研究,其中10项研究均为亚洲人群。包括病例3597例,对照2748例。分析结果显示:(1)VEGF Rs3025039 T/C等位基因、TT/CC基因型、遗传显性模式和隐性模式的合并OR值以及95%CI分别是1.25(1.15~1.37)、1.38(1.08~1.76)、1.26(1.03~1.54)和1.33(1.06~1.68),均P0.05;(2)杂合基因型CT相对于CC的合并OR值及95%CI为1.12(0.86~1.46),P=0.40;(3)在显性模式下,脑梗死组纳入7项研究(OR=1.31,95%CI 1.01~1.70),脑出血组纳入3项研究(OR=1.09,95%CI 0.68~1.73),大动脉粥样硬化型组纳入3项研究(OR=1.36,95%CI 0.74~2.51),小动脉闭塞型组纳入4项研究(OR=1.25,95%CI 0.90~1.73),均P0.05。结论 VEGF Rs3025039 T位点多态性可能增加脑卒中风险,特别在中国等亚洲人群中。     

Handedness in preterm born children: a systematic review and a meta-analysis

It has been proposed that left and/or non-right handedness (NRH) is over-represented in children with a history of preterm birth because such births are associated with a greater incidence of insult to the brain. We report an approximate two-fold increase in left and/or non-right handedness based on a systematic search of the literature from 1980 to September 2010 for English-language articles reporting handedness status in preterm children compared with fullterm controls either as a main focus of the study or as a secondary finding. In total, thirty articles met the inclusion criteria. However, there was a great variation between the included studies in terms of objectives, population characteristics, sample size and methodologies used. While the majority of studies reported a higher incidence of NRH in preterm than fullterm children, this was not a consistent finding. A quality assessment was made to explore the differences in overall study quality and handedness assessment methodology between studies. A random-effects model meta-analysis was then performed to estimate the accumulated effect of preterm birth on handedness (18 studies; 1947 cases and 8170 controls). Preterm children displayed a significantly higher occurrence of NRH than fullterm children (odds ratio [OR]: 2.12; 95% confidence interval [CI]: 1.59-2.78). Sources of heterogeneity were investigated by supplementary meta-analyses considering studies with high or low overall and handedness assessment quality. Publication bias was assessed by Egger's test of the intercept and Duvall and Tweedie's trim-and-fill method. The outcomes of these procedures did not jeopardize the overall finding of reliably increased OR for NRH in preterm children. The present review suggests that a preterm birth is indeed associated with a greater than two-fold likelihood of NRH. Several studies also explored the relationship between handedness and neuropsychological functioning (cognition mainly) with an array of methods. Although not without disagreement, this association was found to be concordant. Studying handedness in preterm children, therefore, is a potentially important index of hemispheric organization and cognitive and sensory-motor functions following neurodevelopmental disturbance.     

Melatonin in autism spectrum disorders: a systematic review and meta-analysis

Aim The aim of this study was to investigate melatonin‐related findings in autism spectrum disorders (ASD), including autistic disorder, Asperger syndrome, Rett syndrome, and pervasive developmental disorders, not otherwise specified. Method Comprehensive searches were conducted in the PubMed, Google Scholar, CINAHL, EMBASE, Scopus, and ERIC databases from their inception to October 2010. Two reviewers independently assessed 35 studies that met the inclusion criteria. Of these, meta‐analysis was performed on five randomized double‐blind, placebo‐controlled studies, and the quality of these trials was assessed using the Downs and Black checklist. Results Nine studies measured melatonin or melatonin metabolites in ASD and all reported at least one abnormality, including an abnormal melatonin circadian rhythm in four studies, below average physiological levels of melatonin and/or melatonin derivates in seven studies, and a positive correlation between these levels and autistic behaviors in four studies. Five studies reported gene abnormalities that could contribute to decreased melatonin production or adversely affect melatonin receptor function in a small percentage of children with ASD. Six studies reported improved daytime behavior with melatonin use. Eighteen studies on melatonin treatment in ASD were identified; these studies reported improvements in sleep duration, sleep onset latency, and night‐time awakenings. Five of these studies were randomized double‐blind, placebo‐controlled crossover studies; two of the studies contained blended samples of children with ASD and other developmental disorders, but only data for children with ASD were used in the meta‐analysis. The meta‐analysis found significant improvements with large effect sizes in sleep duration (73min compared with baseline, Hedge’s g 1.97 [95% confidence interval {CI} CI 1.10–2.84], Glass’s Δ 1.54 [95% CI 0.64–2.44]; 44min compared with placebo, Hedge’s g 1.07 [95% CI 0.49–1.65], Glass’s Δ 0.93 [95% CI 0.33–1.53]) and sleep onset latency (66min compared with baseline, Hedge’s g−2.42 [95% CI −1.67 to −3.17], Glass’s Δ−2.18 [95% CI −1.58 to −2.76]; 39min compared with placebo, Hedge’s g−2.46 [95% CI −1.96 to −2.98], Glass’s Δ−1.28 [95% CI −0.67 to −1.89]) but not in night‐time awakenings. The effect size varied significantly across studies but funnel plots did not indicate publication bias. The reported side effects of melatonin were minimal to none. Some studies were affected by limitations, including small sample sizes and variability in the protocols that measured changes in sleep parameters. Interpretation Melatonin administration in ASD is associated with improved sleep parameters, better daytime behavior, and minimal side effects. Additional studies of melatonin would be helpful to confirm and expand on these findings.     

Retina thickness in atypical parkinsonism: a systematic review and meta-analysis

Journal of Neurology - To investigate the retina thickness assessed using optical coherence tomography in atypical parkinsonism in comparison with health controls (HC) and patients with...     

Neuronal surface autoantibodies in dementia: a systematic review and meta-analysis

Journal of Neurology - Neuronal antibodies can cause encephalopathy syndromes often presenting with subacute cognitive impairment, sometimes resembling neurodegenerative dementias. We searched...     

Survival analysis for valproic acid use in adult glioblastoma multiforme: A meta-analysis of individual patient data and a systematic review

PurposeGlioblastoma multiforme (GBM) is the most lethal type of primary brain tumor, and patients that undergo the maximum tumor resection that is safely possible and standard radiochemotherapy only achieve a median survival time of 14.6 months. Several clinical studies have reported that valproic acid could prolong survival of GBM patients. However, the results of these studies are inconsistent. We examined relevant studies and conducted a meta-analysis to assess the effects of VPA on survival times and recurrence.MethodsA bibliographic search was performed in the EMBASE, MEDLINE, ClinicalTrials.gov and Cochrane Central Register of the Controlled Trials databases to identify potentially relevant articles or conference abstracts that investigated the effects of VPA on the outcome of glioma patients. Five observational studies were included.ResultsPooled estimates of the hazard ratio (HR) and 95% confidence intervals (CI) were calculated. Our meta-analysis confirmed the benefit of using VPA (HR, 0.56; 95% CI, 0.44–0.71). Sub-group analysis shows that patients treated with VPA had a hazard ratio of 0.74 with a 95% confidence interval of 0.59–0.94 vs. patients treated by other-AEDs and a hazard ratio of 0.66 with a 95% confidence interval of 0.52–0.84 vs. patients treated by administration of non-AEDs. No heterogeneity was observed in the subset analysis.ConclusionThe results of our study suggest that glioblastoma patients may experience prolonged survival due to VPA administration. Sub-analysis confirmed the benefit of VPA use compared to a non-AEDs group and an other-AEDs group. Further RCTs of this subject should be performed.     

Glutamatergic drugs for schizophrenia: a systematic review and meta-analysis

OBJECTIVE: To evaluate the efficacy of glutamatergic drugs, acting agonistically on the N-methyl-D-aspartate (NMDA) or the non-NMDA receptors, in schizophrenia. METHOD: All relevant randomized controlled trials of glutamatergic drugs for schizophrenia were obtained from the Cochrane Schizophrenia Group's Register of Trials without any language or year limitations. Trials were classified according to their methodological quality. For binary and continuous data, relative risks and weighted (WMD) or standardized mean differences (SMD) were calculated, respectively. RESULTS: Eighteen short-term trials with 343 randomized patients were included in the meta-analysis. In all of these trials, glycine, D-serine, D-cycloserine or ampakine CX516 was used to augment antipsychotics. NMDA receptor co-agonists glycine and D-serine are effective in reducing negative symptoms (N = 132, fixed effect model SMD = -0.66, 95% CI -1.02 to -0.29, p = 0.0004) of schizophrenia, the magnitude of the effect is moderate. D-Cycloserine, a partial agonist of NMDA receptors, is less effective towards negative symptoms (N = 119, fixed effect model SMD = -0.11, 95% CI -0.48 to 0.25, p = 0.6). Positive symptoms fail to respond to glutamatergic medication. Available derived data on cognitive functioning do not indicate a significant effect of glycine or D-serine (N = 80, random effect model WMD = -2.79, 95% CI -6.17 to 0.60, p = 0.11). CONCLUSIONS: In the current limited data set, a moderate amelioration of negative symptoms of schizophrenia was found, but no other statistically significant beneficial effects on symptoms of schizophrenia.     

Prevalence of tic disorders: a systematic review and meta-analysis

This study evaluated the prevalence of tic disorders. MEDLINE and EMBASE databases were searched, using terms specific to Tourette syndrome and tic disorders, for studies of incidence, prevalence, and epidemiology. Thirty-five studies reporting data from 1985-2011 on the incidence or prevalence of tic disorders in a defined population were included. One reported incidence, and 34 reported prevalence. Meta-analysis of 13 studies of children yielded a prevalence of Tourette syndrome at 0.77% (95% confidence interval, 0.39-1.51%). Prevalence is higher in boys: 1.06% of boys were affected (95% confidence interval, 0.54-2.09%) vs 0.25% of girls (95% confidence interval, 0.05-1.20%). Transient tic disorder comprised the most common tic disorder in children, affecting 2.99% (95% confidence interval, 1.60-5.61%). Meta-analysis of two studies assessing adults for Tourette syndrome revealed a prevalence of 0.05% (95% confidence interval, 0.03-0.08%). The prevalence of tic disorders was higher in all studies performed in special education populations. Tic disorders are more common in children than adults, in boys than girls, and in special education populations. Parents, educators, healthcare professionals, and administrators should be aware of the frequency with which tic disorders occur, and ensure proper access to appropriate care.     

Semantic priming in schizophrenia: systematic review and meta-analysis

BACKGROUND: Increased semantic priming is an influential theory of thought disorder in schizophrenia. However, studies to date have had conflicting findings. AIMS: To investigate semantic memory in patients with schizophrenia with and without thought disorder. METHOD: Data were pooled from 36 studies comparing patients with schizophrenia and normal controls in semantic priming tasks. Data from 18 studies comparing patients with thought disorder with normal controls, and 13 studies comparing patients with and without thought disorder were also pooled. RESULTS: There was no support for altered semantic priming in schizophrenia as a whole. Increased semantic priming in patients with thought disorder was supported, but this was significant only in comparison with normal controls and not in comparison with patients without thought disorder. Stimulus onset asynchrony (SOA) and general slowing of reaction time moderated the effect size for priming in patients with thought disorder. CONCLUSIONS: Meta-analysis provides qualified support for increased semantic priming as a psychological abnormality underlying thought disorder. However, the possibility that the effect is an artefact of general slowing of reaction time in schizophrenia has not been excluded.     

Decreased serum magnesium levels in depression: a systematic review and meta-analysis

Abstract

Background: Magnesium (Mg²⁺), an endogenous N-methyl-D-aspartate receptor antagonist, has received increased attention recently because of its role in the pathophysiology of and treatment response in depression. However, whether Mg²⁺ level is decreased in depression is not firmly established. We aimed to conduct a systematic review and meta-analysis to help making consensus for the association between Mg²⁺ levels and depression.

Methods: A systematic search was conducted in the electronic database resources PubMed and Embase. After a careful selection of relevant studies, a meta-analysis using the random effects model was conducted in each measuring source, such as serum, plasma, and cerebrospinal fluid (CSF).

Results: A total of 18 studies were included in this study. Among 11 studies that measured Mg²⁺ in the serum, Mg²⁺ level was lower in patients with depression than in controls (weighted mean difference =??.088, 95% confidence interval =??.164 to ?.012). In the sensitivity analysis by removing studies one by one, 2 out of the 11 studies obliterated such significant differences. There were no significant differences in the Mg²⁺ levels in the studies for plasma and CSF.

Conclusions: Despite some evidence supporting an association between decreased Mg²⁺ levels and depression from studies with serum, the results of our meta-analysis urge to use caution when associating Mg²⁺ levels and depression. Future studies are needed to establish a consensus for the role of low Mg²⁺ levels in depression.     

Cerebrospinal fluid orexin in Alzheimer's disease: a systematic review and meta-analysis

Objective/backgroundA growing body of evidence suggests that sleep and Alzheimer's disease (AD) have a bi-directional relationship. Emerging research also suggests that orexin, a key neurotransmitter involved in sleep-wake regulation, may be altered in persons with AD, however results have not been consistent across prior studies. This investigation was conducted to both evaluate the aggregate literature to minimize the risk of bias and identify potential factors associated with heterogeneity across studies.MethodsSystematic review identified relevant investigations that compared cerebrospinal fluid orexin in persons with AD and controls. Meta-analysis (random effects model) compared effect size (Hedge's g) for orexin between AD and controls. Meta-regression was additionally performed for key variables of interest to evaluate potential causes of heterogeneity among studies.Results17 studies were identified that met inclusion/exclusion criteria. Evidence of publication bias was not identified. Non-significant increases in orexin were observed in AD relative to controls, with moderate to large heterogeneity among studies (Hedge's g = 0.20, p = 0.136, I² = 72.6%). Meta-regression demonstrated both year of publication (β = 0.055, p = 0.020) and effect size for phosphorylated tau in AD versus controls (β = 0.417, p = 0.031) were associated with differences in orexin.ConclusionsResults do not support broad differences in orexin in AD compared to controls, however, evolving diagnostic criteria may have affected findings across studies. Future research that examines orexin in AD over the longitudinal course of the disorder and explores potential links between phosphorylated tau and orexin are indicated.     

Nocturnal sleep architecture in idiopathic hypersomnia: a systematic review and meta-analysis

BackgroundCurrent sleep medicine nosology places increased importance on nocturnal polysomnographic sleep recordings in the diagnosis of central nervous system disorders of hypersomnolence, particularly idiopathic hypersomnia (IH).ObjectiveDetermine what differences in sleep staging and architecture exist between IH and healthy controls using meta-analysis.MethodsSystematic review identified relevant studies that included nocturnal polysomnography data for IH and healthy control groups. Meta-analysis compared standardized mean differences (Hedge's g) for total sleep time (TST), sleep onset latency (SOL), sleep efficiency (SE), rapid eye movement (REM) sleep percentage, slow wave sleep (SWS) percentage, and REM latency (REML). Moderator analyses were also conducted for variables with significant heterogeneity among studies.ResultsThe meta-analysis included 10 studies. Relative to controls, IH demonstrated increased TST (pooled g = 0.92; 95% CI: 0.46 to 1.38, p < 0.0001) and REM percentage (pooled g = 0.36, 95% CI: 0.09 to 0.64, p = 0.01), decreased SOL (pooled g = −0.46; 95% CI: −0.81 to −0.12, p = 0.009) and SWS percentage (pooled g = −0.28, 95% CI: −0.50 to −0.07, p = 0.01), without significant differences in SE (pooled g = 0.03; 95% CI: −0.32 to 0.38, p = 0.86) or REML (pooled g = 0.14, 95% CI: −0.21 to 0.49, p = 0.42). Moderator analysis demonstrated a significant effect of sex on SE, with a higher proportion of women to men significantly predicting lower SE between in IH and controls (p < 0.0001).ConclusionsIH is associated with several changes in sleep staging and architecture relative to healthy persons, including alterations in REM and SWS not currently delineated in nosological constructs. Further research is indicated to clarify how these findings are related the pathophysiology of IH and related disorders.