Junpeng Ma

Adjunctive brivaracetam for patients with refractory partial seizures: A meta-analysis of randomized placebo-controlled trials

OBJECTIVE To evaluate the clinical efficacy and safety of the newer antiepileptic drug (AED), brivaracetam (BRV), as adjunctive therapy for adults with refractory partial seizures. METHODS Randomized-controlled trials (RCTs) of BRV in the treatment of refractory partial seizure were systematically reviewed and quantified using fixed- or random-effects meta-analysis. 50% responder rate, seizure free rate and adverse events in the treatment period were analyzed as outcomes for measuring efficacy and safety. Pooled effects of risk ratio (RR) and 95% confidence interval (CI) were derived from meta-analysis implemented in RevMan 5.2. RESULTS Five RCTs were identified for inclusion, and included a total of 1639 patients. The pooled RR of BRV vs. placebo as adjunctive therapy for adults with refractory partial seizure was 1.80 (95% CI 1.43-2.26, P < 0.00001) for 50% responder rates, 4.11 (95% CI 1.39-12.21, P = 0.01) for seizure free rates, 1.08 (95% CI 0.73-1.59; P = 0.70) for withdrawal rates. There was no evidence of a statistically significant association between the use of BRV and most adverse events, except somnolence (RR 1.63, 95% CI 1.08-2.45, P = 0.02) and fatigue (RR 2.05, 95% CI 1.19-3.53, P = 0.009). CONCLUSION This study confirmed significant effects of BRV as adjunctive treatment of refractory partial seizures. This study also demonstrated the good tolerability profile of adjunctive BRV for patients with epilepsy. Further large clinical and pharmacovigilance studies are needed to investigate the long-term efficacy and safety of BRV and, furthermore, to suggest an optimal BRV dosage for clinical use.

RNF213 polymorphism and Moyamoya disease: A systematic review and meta-analysis

BACKGROUND Recent genome-wide and locus-specific association studies identified RNF213 as an important Moyamoya disease (MMD) susceptibility gene. But the results of these studies are limited by the few subjects, different methodologies and ethnicities. AIMS To investigate the association between p.R4810K (rs 112735431, ss179362673; G > A) and p.R4859K (c.14576 G > A) polymorphisms of the RNF213 gene and MMD susceptibility. SETTINGS AND DESIGN We conducted a meta-analysis to evaluate the association. MATERIALS AND METHODS Two investigators independently searched the PubMed, Medline, and Embase databases for studies published before October 2012. For included studies, we performed meta-analyses using Cochrane RevMan software. STATISTICAL ANALYSIS Summary odds ratios (ORs) and 95% confidence intervals (CIs) for RNF213 p.R4810K and p.R4859K polymorphisms; MMD were calculated in a fixed-effects model and a random effects model whenever appropriate. RESULTS Five eligible studies were reviewed and analyzed, which included two studies for p.R4810K polymorphisms (421 cases and 1214 controls) and three studies for p.R4859K polymorphisms (398 cases and 765 controls). Overall, the pooled results indicated that both p.R4810K polymorphisms and p.R4859K polymorphisms were associated with MMD risk (OR 92.03, 95% CI 54.06-156.65, P < 0.00001 and OR 157.53, 95% CI 85.37-290.7, P < 0.00001, respectively). Stratified analyses by ethnicity revealed the population attributable risks in the Japanese and Korean populations were larger than that in the Chinese population (P =0.0006). CONCLUSIONS This meta-analysis demonstrated that there are strong associations between p.R4859K and p.R4810K polymorphisms of the RNF213 gene and MMD. The discoveries of its association with MMD may help in early diagnosis and prevention of this disease. Further study is still necessary to clarify the biochemical function and pathological role of RNF213 in MMD.

Endothelin-receptor antagonists for aneurysmal subarachnoid hemorrhage: an updated meta- analysis of randomized controlled trials

IntroductionThe previous meta-analysis on the use of endothelin-receptor antagonists (ETRAs) to treat aneurysmal subarachnoid hemorrhage (SAH) has become outdated due to recently published phase 3 clinical trials. An up-to-date meta-analysis is needed to provide the best available evidence for the efficacy of ETRAs for aneurysmal SAH.MethodsWe performed a systematic review and meta-analysis of published randomized controlled trials that investigate efficacy of ETRAs in patients with aneurysmal SAH. Mortality, unfavorable outcome, delayed ischemic neurological deficit (DIND), delayed cerebral infarction (DCI), angiographic vasospasm and adverse events were analyzed. Meta-analysis was performed in terms of the risk ratio (RR) and 95% confidence interval (CI).ResultsFive eligible studies were reviewed and analyzed, involving 2,595 patients. The pooled RRs of mortality and unfavorable outcome after SAH were 1.03 (95% CI = 0.77 to 1.36) and 1.07 (95% CI = 0.93 to 1.22), respectively. The pooled RRs were 0.87 (95% CI = 0.74 to 1.03) for DCI, 0.77 (95% CI = 0.66 to 0.90) for DIND, and 0.66 (95% CI = 0.57 to 0.77) for angiographic vasospasm. There were significant increases in lung complications (RR = 1.80, 95% CI = 1.55 to 2.09), hypotension (RR = 2.42, 95% CI = 1.78 to 3.29) and anemia (RR = 1.47, 95% CI = 1.19 to 1.83) in patients administered ETRAs.ConclusionThere is no evidence that ETRAs could benefit clinical outcome in patients with SAH. Owing to the increased adverse events, further clinical trials of ETRAs in SAH patients should be more carefully formulated and designed. The present results also suggest that DCI may be a better outcome measure than vasospasm and DIND in SAH clinical trials and observational studies.

Cerebellar tonsillectomy with suboccipital decompression and duraplasty by small incision for Chiari I malformation (with syringomyelia): long term follow-up of 76 surgically treated cases.

AIM To explore the surgical effect of cerebellar tonsillectomy with suboccipital decompression and duraplasty by small surgical incision (3~4cm around the foramina magnum) on treating Chiari I Malformation (CM I) patients. MATERIAL AND METHODS A retrospective study was undertaken on 76 CM I patients treated by this surgery. The surgical efficacy on clinical symptoms and syringomyelia were overall evaluated and analyzed. RESULTS The study included 76 cases (36 men and 40 women; age range, 5-58 years; mean age at surgery, 38.8 years). Preoperative MRI confirmed 56 cases associated with syringomyelia. The follow-up period ranged from 25 to 58 months (median, 46 months). At the end of follow-up, 61 patients (80.26%) had improved, 12 patients (15.79%) were stabilized, and 3 patients (3.95%) had worsened. In MRI scan, syrinx of 55 patients (98.21%) had improved or stabilized compare with syrinx growth in only one patient (1.79%). Statistical analysis reveal the surgical effect tend to be much better in patients with short duration of preoperative symptoms (P=0.001). CONCLUSION Cerebellar tonsillectomy with suboccipital decompression and duraplasty can provide long-time cure for most CM I cases. Early diagnosis and surgery is necessary to improve the surgical effect. A 3~4cm incision around foramen magnum is enough for these operations and may be conducive to reduce postoperative complications.

Effects of Intensive Blood Pressure Lowering on Intracerebral Hemorrhage Outcomes: A Meta-Analysis of Randomized Controlled Trials

AIM Elevation of blood pressure (BP) is common after intracerebral hemorrhage (ICH). Early BP treatment may be beneficial after ICH, but the effect of intensive BP lowering on ICH outcomes is not known and no systematic review or meta-analysis was published regarding this issue. MATERIAL AND METHODS We conducted a meta-analysis to compare the effect of more versus less intensive BP targets on clinical outcomes in patients with ICH. Mortality, unfavorable outcome and adverse events were analyzed. Meta-analysis was performed in terms of the odds ratio (OR) and 95% confidence interval (CI). RESULTS Five eligible studies were included and analyzed, involving 3243 patients to use systolic BP (SBP) < 140 mmHg as target BP and 142 patients to use other BP target in intensive BP target group. The pooled OR of mortality and unfavorable outcome after ICH in intensive BP control group comparing with less intensive BP targets group were 0.99 (95% CI 0.81 to 1.23) and 0.90 (95% CI 0.78 to 1.03) respectively. The pooled OR were 0.97 (95% CI 0.80 to 1.18) for neurological deterioration and 0.83 (95% CI 0.61 to 1.11) for hematoma expansion. There is no difference in other adverse events between two groups. CONCLUSION Acute lowering of SBP to 140 mmHg is probably beneficial for functional outcome in patients with ICH, but the evidence is still insufficient. Further large multicenter studies are required to enhance the evidence to guide the BP lowering target following ICH.

The angiotensin converting enzyme insertion/deletion polymorphism and intracranial aneurysm: a meta-analysis of case-control studies.

CONTEXT Previous studies investigating the association between angiotensin converting enzyme (ACE) insertion (I)/deletion (D) polymorphism and intracranial aneurysm (IA) have provided inconsistent results and no large systematic review or meta-analyses have been conducted regarding this issue. AIM To confirm whether the ACE I/D polymorphism correlates with risk of IA. SETTINGS AND DESIGN We conducted a meta-analysis to increase the statistical power by using all the available published data. MATERIALS AND METHODS Two investigators independently searched the PubMed, Medline, Embase, China National Knowledge Infrastructure and Chinese Biomedicine Databases for studies published before December 2012. For included studies, we performed meta-analyses using the Cochrane RevMan software. STATISTICAL ANALYSIS Summary odds ratios (ORs) and 95% confidence intervals (CIs) for ACE I/D polymorphisms and IA were calculated in a fixed-effects model or a random-effects model when appropriate. We used Cochrans Q statistic and the I 2 statistic to assess heterogeneity and funnel plot to assess potential publication bias. We also carried out stratified analyses and sensitivity analyses by ethnicity, country and source of control group, sample size and Hardy-Weinberg equilibrium (HWE) in controls. RESULTS Six eligible studies were reviewed and analyzed, involving 854 cases and 1280 controls. Overall, compared with D allele, there was a close relationship between I allele and IA risk (OR: 1.21, 95% CI: 1.07-1.37, P = 0.003; P(heterogeneity) = 0.56; I² = 0%). ACE I+ (I/I and I/D) genotype had significantly increased risk for IA (OR: 1.27, 95% CI: 1.03-1.57, P = 0.03; P(heterogeneity) = 0.14; I² = 40%). This association remained consistently strong when analyses were limited to studies, in which genotype frequencies were in HWE. No publication bias was found in the present study. CONCLUSIONS Our meta-analysis suggests, there is a close relationship between ACE I/D polymorphism and IA risk. Since limited studies and subjects were included, it is critical that larger and especially well-designed multicentric studies, which based on interactions of ACE and different confounding factors should be performed to re-evaluate the association.

Diagnosing residual or recurrent cerebral aneurysms after clipping by computed tomographic angiography: Meta-analysis.

BACKGROUND A cerebral aneurysm with incomplete treatment may re-grow and cause new bleeding. This meta-analysis calculates the sensitivity and specificity of computed tomographic angiography (CTA) in the detection of the residual or recurrent cerebral aneurysms after clipping, in comparison with digital subtraction angiography (DSA). MATERIALS AND METHODS Between October 1997 and October 2012, relevant data were systematically and prospectively collected without language restrictions from the PUBMED and EMBASE databases for analysis. A total of 10 eligible studies compared CTA with DSA in the detection of the residual or recurrent cerebral aneurysms after clipping by two independent observers. The sensitivity, specificity, positive likelihood ratio (+LR), and negative likelihood ratio (-LR) were calculated on a per-aneurysm basis, and the area under the sROC curve (AUC), heterogeneity, and publication bias also were evaluated. RESULTS A total of 487 aneurysms were included for meta-analysis. The pooled sensitivity, specificity, +LR, -LR, DOR, and AUC of CTA for detecting the residual or recurrent aneurysms after clipping were 71%, 94%, 9.39, 0.32, 28.32, and 0.8558, respectively. The between-study heterogeneity of DOR and the presence of publication bias were not statistically significant. CONCLUSIONS As a noninvasive and convenient screening method, CTA has a high diagnostic value for the detection of the residual or recurrent aneurysms after clipping. In the future, it may be used as a routine diagnostic tool for evaluation of aneurysms after clipping.

Endoscopic surgery versus conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage (ECMOH): study protocol for a randomized controlled trial

BackgroundSpontaneous intracerebral hemorrhage is a disease with high morbidity, high disability rate, high mortality, and high economic burden. Whether patients can benefit from surgical evacuation of hematomas is still controversial, especially for those with moderate-volume hematomas in the basal ganglia. This study is designed to compare the efficacy of endoscopic surgery and conservative treatment for the moderate-volume hematoma in spontaneous basal ganglia hemorrhage.MethodsPatients meet the criteria will be randomized into the endoscopic surgery group (endoscopic surgery for hematoma evacuation and the best medical treatment) or the conservative treatment group (the best medical treatment). Patients will be followed up at 1, 3, and 6 months after initial treatment. The primary outcomes include the Extended Glasgow Outcome Scale and the Modified Rankin Scale. The secondary outcomes consist of the National Institutes of Health Stroke Scale and the mortality. The Barthel Index(BI) will also be evaluated. The sample size is 100 patients.DiscussionThe ECMOH trial is a randomized controlled trial designed to evaluate if endoscopic surgery is better than conservative treatment for patients with moderate-volume hematomas in the basal ganglia.Trial registrationChinese Clinical Trial Registry: ChiCTR-TRC-11001614(http://www.chictr.org/en/proj/show.aspx?proj=1618)

Is decompressive craniectomy useless in severe traumatic brain injury

Recently, a multicenter randomized controlled trial (RCT) by Cooper and colleagues indicated that decompressive craniectomy (DC) may be associated with a worse functional outcome in patients with diffuse traumatic brain injury (TBI), although DC can immediately and constantly reduce intracranial pressure (ICP). As this trial is well planned and of high quality, the unexpected result is meaningful. However, the evidence of the study is insufficient and the effect of DC in severe TBI is still uncertain. Additional multicenter RCTs are necessary to provide class I evidence on the role of DC in the treatment of refractory raised ICP after severe TBI.

Accuracy of computed tomography angiography in detecting the underlying vascular abnormalities for spontaneous intracerebral hemorrhage: A comparative study and meta-analysis

BACKGROUND Computed tomography angiography (CTA) is a rapid, non-invasive procedure with a small risk for evaluating patients with various types of strokes. But the effectiveness of CTA in detecting the etiology of spontaneous intracerebral hemorrhage (SICH) has not been well established. AIM To evaluate the diagnostic value of CTA for detecting underlying vascular abnormalities in patients with SICH. SETTINGS AND DESIGN This is a comparative study to evaluate the diagnostic accuracy of CTA and digital subtraction angiography (DSA) in SICH. We also did a meta-analysis, combining our results with those of all previous studies to determine a more precise estimate of CTA in detecting the etiology of SICH.. MATERIALS AND METHODS Between July 2009 and October 2011, CTA and DSA were routinely performed in consecutive young patients (age between 18 and 45 years) with acute non-hypertensive SICH. Imaging data were prospectively stored in the database for analysis. STATISTICAL ANALYSIS The sensitivity, specificity, positive predictive values (PPV), negative predictive values (NPV), and accuracy were used for evaluating the diagnostic value of CTA for vascular lesion. RESULTS This study included 92 patients. The sensitivity, specificity, PPV, NPV, and accuracy of CTA for detecting DSA-positive pathologies were 94.6%, 100%, 100%, 96.5%, and 97.8%, respectively. A total of 544 cases were included for meta-analysis. The pooled sensitivity, specificity, PPV, NPV, and accuracy of CTA for detecting the etiology in SICH were 95.4%, 98.3%, 96.9%, 97.4%, and 97.2%, respectively. There was no substantial heterogeneity between the studies. CONCLUSIONS CTA has high PPV and NPV for vascular pathologies. It should be performed as the initial vascular investigation for patients with acute SICH. Future technical advancement of CTA is still needed to eliminate the false-negative results.