Perioperative management of antithrombotics in elective intracranial procedures: systematic review, critical appraisal.

PURPOSE: Perioperative management of patients medicated with antithrombotics requiring elective intracranial procedures is challenging. We ought to (1) identify the clinical practice guidelines (CPGs) and recommendations (CPRs) on perioperative management of antithrombotic agents in elective intracranial surgery and (2) assess their methodological quality and reporting clarity. METHODS: The study was conducted following the 2020 PRISMA guidelines for a systematic review and has been registered (PROSPERO, CRD42023415710). An electronic search was conducted using PubMed, Scopus, and Google Scholar. The search terms used were "adults," "antiplatelets," "anticoagulants," "guidelines," "recommendations," "english language," "cranial surgery," "brain surgery," "risk of bleeding," "risk of coagulation," and "perioperative management" in all possible combinations. The search period extended from 1964 to April 2023 and was limited to literature published in the English language. The eligible studies were evaluated by three blinded raters, by employing the Appraisal of Guidelines for Research & Evaluation II (AGREE-II) analysis tool. RESULTS: A total of 14 sets of guidelines were evaluated. Two guidelines from the European Society of Anaesthesiology and one from the American College of Chest Physicians found to have the highest methodological quality and reporting clarity according to the AGREE-II tool. The interrater agreement was good with a mean Cohens Kappa of 0.70 (range, 46.5-94.4%) in the current analysis. CONCLUSION: The perioperative management of antithrombotics in intracranial procedures may be challenging, complex, and demanding. Due to the lack of high quality data, uncertainty remains regarding the optimal practices to balance the risk of thromboembolism against that of bleeding.

Systematic Review on Early and Follow-up Mortality Rate in Octogenarians Treated With a Fenestrated and/or Branched Endovascular Aortic Repair.

PURPOSE: Advanced age has been related to conflicting outcomes after fenestrated/branched endovascular aortic aneurysm repair (F/BEVAR). The aim of this meta-analysis is to compare 30-day mortality, technical success, and 1-year and 5-year survival in octogenarians and non-octogenarians who underwent F/BEVAR for complex aortic aneurysms. MATERIALS AND METHODS: This meta-analysis was pre-registered to PROSPERO (CRD42022348659). The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) 2020 statement was followed. A search of the English literature, via Ovid, using MEDLINE, Embase, and CENTRAL databases, until August 30, 2022, was executed. Randomized Control Trials and observational studies (2000-2022), with ≥5 patients, reporting on 30-day mortality and 1-year and 5-year survival rates among octogenarians and non-octogenarians after F/BEVAR were eligible. The Risk Of Bias In Non-Randomized Studies of Interventions (ROBINS-I) tool was applied to assess the risk of bias. The primary outcome was 30-day mortality and secondary was 1-year and 5-year survival in octogenarians and non-octogenarians. The outcomes were summarized as odds ratio (OR) with 95% confidence intervals (CIs). A narrative presentation was selected in case of missing outcomes. RESULTS: The initial research isolated 3263 articles; 6 retrospective studies were finally included. A total of 7410 patients were managed with F/BEVAR; 1499 patients (20.2%) were ≥80 years old (75.5% males, 259/343). The estimated 30-day mortality was 6% among octogenarians vs 2% in younger patients, with a significantly higher 30-day mortality for patients ≥80 years old (OR 1.21, 95% CI 0.61-1.81; p=0.0.11; Ι2=36.01%). Technical success was similar between the groups (OR -0.83; 95% CI -1.74-0.07, p<0.0.001; Ι2=95.8%). Regarding survival, a narrative approach was decided due to missing data. Two studies reported a statistically significant difference in 1-year survival between groups, with higher mortality in octogenarians (82.5%-90% vs 89.5%-93%), while 3 reported a similar 1-year survival rate in both groups (87.1%-95% vs 88%-89.5%). At 5 years, 3 studies reported a statistically significant lower survival for octogenarians (26.9%-42% vs 61%-71%). CONCLUSIONS: Octogenarians treated with F/BEVAR presented higher 30-day mortality while a lower survival rate at 1 and 5 years was reported in the literature. Patient selection is thus mandatory among older patients. Further studies, especially on patient risk stratification, are needed to estimate the F/BEVAR outcomes on elder patients. CLINICAL IMPACT: Age may be a factor of increased early and long-term mortality within patients managed for aortic aneurysms. In this analysis, patients over 80 years old were compared to their younger counterparts when managed with fenestrated or branched endovascular aortic repair (F/BEVAR) . The analysis showed that early mortality was acceptable for octogenrains but significantly higher when compared to patients younger than 80 years. One-year survival rates are controversial. At 5-year follow-up, octogenarians present lower survival but data to provide metanalysis are lacking. Patient selection and risk stratification are mandatory in older candidates for F/BEVAR.

Effect of Sarcopenia on Mortality and Spinal Cord Ischaemia After Complex Aortic Aneurysm Repair: Systematic Review and Meta-Analysis.

OBJECTIVE: Sarcopenia has been related to higher mortality rates after abdominal aortic aneurysm repair. This analysis aimed to assess sarcopenia related mortality and spinal cord ischaemia (SCI) at 30 days, and mortality during the available follow up, in patients with complex aortic aneurysms, managed with open or endovascular interventions. DATA SOURCES: A search of the English literature, via Ovid, using Medline, EMBASE, and CENTRAL up to 15 June 2022 was done. REVIEW METHODS: This meta-analysis was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) guidelines and preregistered in PROSPERO (CRD42022338079). Observational studies (2000 - 2022), with five or more patients, reporting on sarcopenia related mortality and SCI at 30 days, and midterm mortality after thoraco-abdominal aneurysm repair (open or endovascular), were eligible. The ROBINS-I tool (Risk Of Bias In Non-Randomised Studies of Interventions) was used for risk of bias, and GRADE (Grading of Recommendations, Assessment, Development and Evaluation) for the assessment of evidence quality. The primary outcome was 30 day and midterm mortality, and the secondary outcome was SCI at 30 days, in sarcopenic and non-sarcopenic patients. The outcomes were summarised as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: Four retrospective studies (1 092 patients; 40.0% sarcopenic) were included. Thirty day mortality was similar, with low certainty between groups (6% [95% CI 1 - 11] in sarcopenic vs. 5% [95% CI 1 - 9] non-sarcopenic patients [OR 0.30, 95% CI -0.21 - 0.81; p = .94, Ι2 = 0%). The estimated midterm mortality was statistically significantly higher (very low certainty) in sarcopenic patients (25% [95% CI 0.19 - 0.31] vs. 13% [95% CI -0.03 - 0.29] in non-sarcopenic patients (1.11 OR 0.95, 95% CI -0.21 - 2.44; p < .001, Ι2 = 88.32%). SCI was significantly higher (very low certainty) in sarcopenic patients (19%, 95% CI 4 - 34) vs. 7% (95% CI 5 - 20) in non-sarcopenic patients (OR 1.80, 95% CI -0.17 - 3.78; Ι2 = 82.4%), despite an equal distribution of aneurysm type between the groups. CONCLUSION: Early mortality does not appear to be affected by sarcopenia in patients treated for thoraco-abdominal aneurysms. However, sarcopenia may be associated with higher peri-operative SCI and midterm mortality rates.

Bilateral Tapia's syndrome secondary to cervical spine injury: a case report and literature review.

A 24-year-old man presented with bilateral Tapia's syndrome (TS) after a traumatic cervical spine injury, manifested by apraxia of the hypoglossal and recurrent laryngeal nerves. The initial presentation was a profound inability to maintain upper respiratory airway patency due to bilateral vocal cord paralysis, accompanied by impairment of swallowing and loss of speech. The diagnosis was based on clinical grounds and verified by endoscopic laryngoscopy. A C7 corpectomy was performed for stabilizing the cervical spine, while conservative treatment with steroids was reserved for the TS. Over the following six months, there was complete resolution of the symptoms.

Conventional cardiovascular risk factors in Transient Global Amnesia: Systematic review and proposition of a novel hypothesis.

Transient Global Amnesia (TGA) is an enigmatic amnestic syndrome. We conducted a systematic review to investigate the relationship between the conventional cardiovascular risk factors and TGA. MEDLINE, CENTRAL, EMBASE and PsycINFO were comprehensively searched and 23 controlled observational studies were retrieved. The prevalence of hypertension, diabetes mellitus, dyslipidemia and smoking was lower among patients with TGA compared to Transient Ischemic Attack. Regarding the comparison of TGA with healthy individuals, there was strong evidence suggesting a protective effect of diabetes mellitus on TGA and weaker evidence for a protective effect of smoking. Hypertension was associated with TGA only in more severe stages, while dyslipidemia was not related. In view of these findings, a novel pathophysiological hypothesis is proposed, in which the functional interactions of Angiotensin-II type-1 and N-methyl-D-aspartate receptors are of pivotal importance. The whole body of clinical evidence (nature of precipitating events, associations with migraine, gender-based association patterns) was integrated.

Editor's Choice - Sex Specific Outcomes After Complex Fenestrated and Branched Endovascular Aortic Repair: A Systematic Review and Meta-analysis.

OBJECTIVE: As females are at higher mortality risk after endovascular aortic repair, this study aimed to compare the 30-day and 12-month mortality, morbidity, and re-intervention rates between the sexes, treated with fenestrated or branched endovascular aortic repair (F/BEVAR). DATA SOURCES: A search of the English literature, via Ovid, using MEDLINE, Embase, and CENTRAL, up to 30 July 2021, was performed. REVIEW METHODS: This meta-analysis was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement, and its protocol was registered in PROSPERO (CRD42021273418). Observational studies (2010-21), with ≥ 20 patients, reporting on sex specific outcomes (mortality, acute kidney injury [AKI], spinal cord ischaemia [SCI], and re-intervention, after F/BEVAR), were considered eligible. Risk of bias in the studies was assessed using ROBINS-I, and evidence quality was assessed using GRADE. The primary outcome was the sex specific 30-day mortality rate, AKI, SCI, and re-intervention rates; secondary outcomes were survival and freedom from re-intervention at 12 months after F/BEVAR. The outcomes were summarised as odds ratio (OR) with 95% confidence intervals (CIs). RESULTS: Four retrospective and one prospective study (2 421 patients; 26% females) were included. The 30-day mortality rate was 12% in females vs. 3% in males (OR 2.65, 95% CI 1.79 - 3.92; Ι2 = 0%). The 30-day AKI, SCI, and re-intervention rates were similar (OR 1.45, 95% CI 1.03 - 2.03; Ι2 = 0%; OR 1.86, 95% CI 1.27 - 2.74; Ι2 = 38%; and OR 1.06, 95% CI 0.66 - 1.77; Ι2 = 0%, respectively). The 12-month survival rate was lower in females (OR 0.95, 95% CI 0.91 - 0.99; Ι2 = 38%). When excluding 30-day deaths, there was no difference in 12-month survival between sexes (OR 0.99, 95% CI 0.95 - 1.02; Ι2 = 32%). The 12-month freedom from re-intervention was similar between sexes (OR 0.87, 95% CI 0.75 - 1.01; Ι2 = 0%). CONCLUSION: Female patients treated by F/BEVAR may present worse outcomes in terms of 30-day and 12-month survival. The high peri-operative mortality rate remains an issue. When excluding 30-day deaths, the 12-month survival rate was similar between the sexes. Early morbidity and re-intervention rates were comparable.

Methodological assessment of guidelines for the diagnosis and management of cerebral vasospasm using the AGREE-II tool.

OBJECTIVE: Rupture of an intracranial aneurysm is the most common cause of spontaneous subarachnoid hemorrhage. Despite the recent advances in its early detection, diagnosis, and proper treatment, the outcome of patients experiencing aneurysmal subarachnoid hemorrhage (aSAH) remains poor. It is well known that cerebral vasospasm is the most troublesome complication of aSAH, while delayed cerebral ischemia related to cerebral vasospasm constitutes the major cause of unfavorable outcomes in patients with aSAH. The need for evidence-based guidelines is of great importance for the prevention, early detection, and efficient management of aSAH-induced vasospasm. Moreover, guidelines provide young physicians with a valuable tool for practicing defensible medicine. However, the methodology, clinical applicability, reporting clarity, and biases of guidelines must be periodically assessed. In this study, the authors sought to assess the reporting clarity and methodological quality of published guidelines and recommendations. METHODS: A search was performed in the PubMed, Scopus, and Web of Science databases. The search terms used were "clinical practice guidelines," "recommendations," "stroke," "subarachnoid hemorrhage," and "vasospasm" in all possible combinations. The search period extended from 1964 to September 2021 and was limited to literature published in the English language. All published guidelines and recommendations reporting on the diagnosis and management of vasospasm were included. Studies other than those reporting guidelines and recommendations were excluded. The eligible studies were evaluated by three blinded raters, employing the Appraisal of Guidelines for Research & Evaluation II (AGREE-II) analysis tool. RESULTS: A total of 10 sets of guidelines were evaluated in this study. The American Heart Association/American Stroke Association issued guidelines found to have the highest methodological quality and reporting clarity, followed by the European Stroke Organization guidelines and the English edition of the Japanese guidelines issued by the Japanese Society on Surgery for Cerebral Stroke. The interrater agreement was moderate in the current analysis. CONCLUSIONS: These findings support the idea that improvement of currently existing guidelines is feasible in the following domains: the rigor of guidelines and recommendations development, clinical applicability, editorial independence, and stakeholder involvement. Furthermore, periodic updating of published guidelines requires improvement in the future.

Neuromonitoring in Severe Traumatic Brain Injury: A Bibliometric Analysis.

Traumatic brain injury (TBI) is the leading cause of mortality and disability among trauma-related injuries. Neuromonitoring plays an essential role in the management and prognosis of patients with severe TBI. Our bibliometric study aimed to identify the knowledge base, define the research front, and outline the social networks on neuromonitoring in severe TBI. We conducted an electronic search for articles related to neuromonitoring in severe TBI in Scopus. A descriptive analysis retrieved evidence on the most productive authors and countries, the most cited articles, the most frequently publishing journals, and the most common author's keywords. Through a three-step network extraction process, we performed a collaboration analysis among universities and countries, a cocitation analysis, and a word cooccurrence analysis. A total of 1884 records formed the basis of our bibliometric study. We recorded an increasing scientific interest in the use of neuromonitoring in severe TBI. Czosnyka, Hutchinson, Menon, Smielewski, and Stocchetti were the most productive authors. The most cited document was a review study by Maas et al. There was an extensive collaboration among universities. The most common keywords were "intracranial pressure," with an increasing interest in magnetic resonance imaging and cerebral perfusion pressure monitoring. Neuromonitoring constitutes an area of active research. The present findings indicate that intracranial pressure monitoring plays a pivotal role in the management of severe TBI. Scientific interest shifts to magnetic resonance imaging and individualized patient care on the basis of optimal cerebral perfusion pressure.

Intermediate surgical outcome in patients suffering poor-grade aneurysmal subarachnoid hemorrhage. A single center experience.

BACKGROUND: It is known that patients suffering poor-grade aneurysmal subarachnoid hemorrhage (aSAH) have a dismal prognosis. The importance of early intervention is well established in the pertinent literature. Our aim was to assess the functional outcome and overall survival of these patients undergoing surgical clipping. MATERIAL AND METHODS: In the current retrospective study we included all consecutive poor-grade patients after spontaneous SAH who presented at our institution over an eight-year period. All participants suffering SAH underwent brain CT angiography (CTA) to identify the source of hemorrhage. We assessed the severity of hemorrhage according to the Fisher grade classification scale. All patients were surgically treated. The functional outcome was evaluated six months after the onset with the Glasgow Outcome Scale. Finally, we performed logistic and Cox regression analyses to identify potential prognostic risk factors. RESULTS: Our study included twenty-three patients with a mean age of 53 years. Five (22%) patients presented with Hunt and Hess grade IV, and eighteen (78%) with grade V. The mean follow-up was 15.8 months, while the overall mortality rate was 48%. The six-month functional outcome was favorable in 6 (26%) patients. The vast majority of our patients died between the 15th and the 60th post-ictal days. We did not identify any statistically significant prognostic factors related to the patient's outcome and/or survival. CONCLUSIONS: Poor-grade aSAH patients may have a favorable outcome with proper surgical management. Large-scale studies are necessary for accurately outlining the prognosis of this entity, and identifying parameters that could be predictive of outcome.

Clinical effect of accessory renal artery coverage after endovascular repair of aneurysms in abdominal and thoracoabdominal aorta.

BACKGROUND: The aim of our systematic review and meta-analysis was to assess the effect of accessory renal artery (ARA) coverage on renal function in terms of acute kidney injury (AKI), renal infarction, chronic renal failure (CRF), and mortality in patients undergoing standard endovascular aortic aneurysm repair (EVAR) or endovascular repair of complex aneurysms. METHODS: An electronic search of the English language medical literature from 2000 to September 2020 was conducted using the MEDLINE, EMBASE, and Cochrane databases with the PRISMA (preferred reporting items for systematic reviews and meta-analyses) method for studies reporting on ARA management in patients undergoing endovascular repair of aneurysms in the abdominal and thoracoabdominal aorta. The patients were divided into two groups: group 1, patients with ARA coverage; and group 2, patients without an ARA or without coverage of the ARA. Each group included two arms, one of patients who had undergone standard EVAR and one of patients who had undergone endovascular treatment of a complex aortic aneurysm. The GRADE (grading of recommendations assessment, development, evaluation) approach was used to evaluate the quality of evidence and summary of the findings. The primary outcomes included the incidence of AKI, renal infarction, CRF, and mortality. RESULTS: Ten retrospective, nonrandomized, control studies were included in the systematic review reporting on 1014 patients (302 with a covered ARA vs 712 without an ARA or without ARA coverage). In six studies, the mean diameter of the covered ARA was <4 mm (range, 2.7-3.4 mm). The mean follow-up was 22.74 months (range, 1-42 months). In the standard EVAR subgroup, the risk of AKI (odds ratio [OR], 0.72; 95% confidence interval [CI], 0.21-2.51; I2 = 0%] in the early period, and CRF (OR, 4.44; 95% CI, 0.46-42.61; I2 = 87%) and death (OR, 0.91; 95% CI, 0.36-2.31; I2 = 0%) during follow-up were similar between groups 1 and 2. Only the risk of renal infarction was greater in group 1 than in group 2 (OR, 93.3; 95% CI, 1.48-5869; I2 = 92%). In the complex aneurysm repair subgroup, the risk of AKI (OR, 1.85; 95% CI, 0.61-5.64; I2 = 42%) in early period and CRF (OR, 1.64; 95% CI, 0.88-3.07; I2 = not applicable) and death (OR, 3.63; 95% CI, 0.14-96.29; I2 = 56%) during follow-up were similar between groups 1 and 2. Only the risk of renal infarction was greater for group 1 compared with group 2 (OR, 8.58; 95% CI, 4.59-16.04; I2 = 0%). CONCLUSIONS: ARA (<4 mm) coverage in patients undergoing standard EVAR or endovascular repair of complex aneurysms is associated with an increased risk of renal infarction. However, we found no clinical effects of ARA coverage on renal function or mortality in early postoperative and follow-up period. Preservation of an ARA >4 mm should be considered.

Serum lipid abnormalities in migraine: A meta-analysis of observational studies.

BACKGROUND: The association of migraine with vascular comorbidities is long-established. The contribution of the "traditional" cardiovascular risk factors to this connection remains unclear. OBJECTIVE: To determine-quantify the differences in the serum lipid concentrations between lipid-lowering agents-naïve individuals with migraine and healthy controls (HC). METHODS: The study protocol was not preregistered with an online systematic review-protocol registry. A literature search involving MEDLINE, EMBASE, CENTRAL, Google Scholar, and the OpenGrey database was performed. Case-control, cross-sectional, or cohort studies involving HC and participants with migraine (with and without aura regardless of the use of prophylactic treatment) that quantitatively assessed serum low-density lipoprotein cholesterol (LDL-C) (primary index) and/or total cholesterol (TC) and/or high-density lipoprotein cholesterol (HDL-C) and/or triglycerides (TG) (secondary indices) were retrieved. Articles including participants with known dyslipidemia (or under lipid-lowering medications) or with secondary causes of dyslipidemia (aside from the subjectively assessed lifestyle parameters) were excluded. Studies with abstracts and full texts not published in English and articles reporting the implementation of other study designs (reviews, meta-analyses, commentaries, case reports, etc.) were excluded as well. Conference abstracts and English abstracts from studies with full texts not published in English were evaluated as part of the gray literature. Each step of the review process was performed by two investigators independently, and relevant data were abstracted based on standardized extraction forms. Any discrepancies were resolved by a third investigator. RESULTS: Seventeen studies (16 case-control and 1 cross-sectional) fulfilled the eligibility criteria. Retrieved articles involved adult participants, principally during the fourth decade of life. Results were compatible with higher LDL-C levels in migraine individuals (1370) than in HC (1215) [12 studies, mean difference (MD) = 10.4 mg/dl, 95% confidence interval (CI) = (1.6, 19.2)]. Similarly, higher TC levels were determined in migraine patients [14 studies, migraine = 1325, HC = 1213, MD = 10.6 mg/dl, 95% CI = (1.8, 19.3)], as were TG levels [15 studies, migraine = 1526, HC = 1262, MD = 11.8 mg/dl, 95% CI = (3.6, 20.0)]. HDL-C concentrations were not different between the two groups [14 studies, migraine = 1488, HC = 1328, MD = -0.4 mg/dl, 95% CI = (-2.2, 1.5)]. Prespecified sensitivity analysis following the exclusion of studies not presenting comparable body mass index values between the groups nullified the significant difference regarding LDL-C levels [MD = 5.3 mg/dl, 95% CI = (-0.1, 10.8)]. Subgroup analyses as well as the direct comparison of migraine with aura and migraine without aura individuals were compatible with no difference regarding lipid concentrations, but only a small fraction of the retrieved studies presented relevant figures. CONCLUSIONS: Although our results are of limited generalizability, since most retrieved studies were performed in Turkey (nine studies), TC abnormalities may provide part of the explanation for the unfavorable cardiovascular profile of migraine patients. Lifestyle may be partly or entirely accountable for the determined increased serum TC. Additional studies that will completely address the effect that lifestyle parameters exert on lipid concentrations are required to better capture existing abnormalities.

The Association of Spondylitis and Aortic Aneurysm Disease.

OBJECTIVES: The aim of this study is to assess any relation between spondylitis and aortic aneurysmal disease by reviewing the current literature. METHODS: A systematic search was undertaken using MEDLINE, EMBASE and CENTRAL databases till May 2019, for articles reporting on patients suffering from spondylitis and aortic aneurysm. RESULTS: The most involved aortic segment was infrarenal aorta (56.9%). The lumbar vertebrae were more frequently affected (79.7%). Commonest symptoms were back pain (79.1%), fever (33.7%) and lower limb pain (29.1%). 55.8% of cases were diagnosed using computed tomography. The pathology was attributed to infectious causes in 25.1% of cases. 53.4% of patients were treated only for the aneurysm, 27.9% for both pathologies, while two patients solely for the vertebral disease. Endovascular aneurysm repair was chosen in 12.8% of cases. The 30-day mortality was 8.1% (7/86); mostly from vascular complications. CONCLUSIONS: A synchronous spondylitis and aortic aneurysm may share common etiopathology, when an infectious or inflammatory cause is presented. The lumbar vertebrae are more frequently affected. Low quality data do not allow safe conclusion to suggest the best treatment option.

Local complications of adjunct intrathecal antibiotics for nosocomial meningitis associated with gram-negative pathogens: a meta-analysis.

Direct delivery of antibiotics to the ventricular system offers an alternative for the management of nosocomial meningitis. However, the available literature frequently results in controversial findings regarding its safety. The present meta-analysis aimed at summarizing the risk of local complications after the administration of intraventricular/intrathecal (IVT/IT) antibiotics for the treatment of ventriculitis/meningitis (VM) associated with gram-negative pathogens. We systematically searched the medical literature from 1964 until July 2018, for clinical studies reporting on complications after the index treatment. The quality of the eligible studies was classified as "high," "moderated," and "low" for randomized controlled trials, observational studies, and case series, respectively. The results were summarized as pooled frequencies, estimated by the random- or fixed-effects models, according to the inter-study heterogeneity. The publication bias was visualized in trim-and-fill funnel plots. Τhe analysis included twenty-three primary studies with 229 patients. The overall complication rate was as high as 0.13 (95% CI 0.08; 0.19, I2 = 9%); chemical meningitis and seizures represented the majority of the complications, with an occurrence rate of 0.11 (95% CI 0.07; 0.17, I2 = 0%) and 0.07 (95% CI 0.04; 0.12; I2 = 0%), respectively. The meta-analysis was based on studies of "moderate" and "low" reporting quality, while the publication bias after inspecting of the funnel plots revealed significant asymmetry. The present review denotes the absence of large, high-quality studies in the field. Nevertheless, IVT/IT was associated with moderate morbidity, mainly attributed to chemical meningitis and seizures. Further high-quality studies are still required before this therapeutic modality becomes broadly established.

Intravenous sodium valproate in status epilepticus: review and Meta-analysis.

Objective: Status epilepticus (SE) is a common neurologic emergency. The present study constitutes a meta-analysis of published randomized control trials (RCTs) evaluating the use of intravenous sodium valproate (VPA) in SE.Methods: MEDLINE and Cochrane databases were comprehensively searched, while retrieved RCTs and meta-analyses were manually screened. Prespecified outcome measures included seizure-cessation, 24 h-efficacy, constitute (liver enzyme increase, arrhythmias, bone-marrow suppression, hypotension and respiratory depression) and severe (life-threatening) adverse events (AEs). Evidence synthesis was performed when appropriate, using Random-Effects (RE) or Fixed-Effects (FE) model based on heterogeneity between trials (homogeneity assumed when PQ > 0.1 and I2 < 50%). Outcomes were assessed using Odds-Ratios (ORs) and 95%Confidence-Intervals (95% CIs). Every available comparison was investigated in terms of efficacy and tolerability.Results:Thirteen studies were retrieved and five comparisons were available, four of which involved two or more studies. Results were compatible with no significant difference between VPA and Phenytoin both in terms of efficacy and tolerability [seizure-cessation: FE-OR = 1.99, 95% CI = (0.83-4.75), 24 h-efficacy: FE-OR = 1.32, 95% CI = (0.60-2.89), composite AEs: FE-OR = 0.45, 95% CI = (0.17-1.21)]. Phenobarbital proved more commonly associated with composite AEs than VPA [seizure-cessation: RE-OR = 0.68, 95% CI = (0.05-9.44), 24 h-efficacy: RE-OR = 0.88, 95% CI = (0.02-33.9), composite AEs: FE-OR = 0.26, 95% CI = (0.09-0.82), severe AEs: FE-OR = 0.30, 95% CI = (0.04-2.28)]. Diazepam was determined inferior to VPA concerning safety issues [seizure-termination: FE-OR = 0.77, 95% CI = (0.34-1.79), severe respiratory depression: FE-OR = 0.06, 95% CI = (0.01-0.48), severe hypotension: FE-OR = 0.09, 95% CI = (0.01-0.72)]. The combination of Lorazepam (LZP) with VPA and the combination of LZP with Levetiracetam presented no difference in efficacy [24h-efficacy: FE-OR = 0.68, 95% CI = (0.37-1.24)].Conclusions: Although, additional high-quality RCTs are warranted, according to our results, VPA can be considered a safe and effective option in the management of SE.

Assessment of TREM2 rs75932628 variant's association with Parkinson's disease in a Greek population and Meta-analysis of current data.

BACKGROUND: Α number of genetic variants are considered to confer susceptibility to Parkinson's disease (PD). Rs75392628 (R47H), a rare variant of TREM2 gene, has been linked to PD, although its role on PD remains conflicting. OBJECTIVE: Detection of a possible contribution of rs75392628 variant of TREM2 gene to PD risk. METHODS: A total of 358 PD patients and 358 healthy controls genotyped for rs75392628. In addition, a meta-analysis was performed by merging our results with those from previous studies. RESULTS: The rare variant of rs75932628 (47H) of TREM2 gene was not detected on cohort. Meta-analysis of a total of 9271 PD cases and 9777 controls across 14 independent PD data sets from 9 studies, including the present study, did not show any statistically significant effect of rs75392628 on PD risk (ORFE:1.54 95% CI:0.87-2.73. ORRE: 1.54, 95%CI: 0.71-3.32). CONCLUSIONS: Rs75392628 TREM2 variant is rather unlikely to be a major genetic risk contributor of PD.

Guidelines on the use of external ventricular drain and its associated complications: do we "AGREE II"?

Insertion of an external ventricular drain is a common procedure used in everyday practice by neurosurgeons all around the world. It consists of the placement of an external ventricular drain (EVD) into the ventricular system providing the ability to measure intracranial pressure, and also divert the flow of cerebrospinal fluid (CSF) in a variety of pathological conditions. The most common complication is infection, and it may result in devastating consequences and negatively affect the outcome of these patients. The Infectious Diseases Society of America (IDSA), the Neurocritical Care Society (NCS), and The Society for Neuroscience in Anesthesiology & Critical Care (SNACC) have published recommendations for the management of EVD-Associated Ventriculitis. The objective of this study was to assess the methodological quality and reporting clarity of these recommendations using the AGREE-II tool. We found that the overall quality of the published clinical practice guidelines is acceptable. However, continuous updates and external validation should be implemented.

The Greek linguistic assessment for awake brain surgery: development process and normative data.

Language mapping with direct electrical stimulation is considered the gold standard in surgical treatment of brain tumors. Assessing a variety of language functions intraoperatively can affect the extent of the tumor resection as well as the patient's postoperative quality of life. Although most tests include preoperative sessions where tasks are personalised to each patient, normative data are essential since they can ensure that the presented stimuli can be responded appropriately. In this study, we describe the development and standardisation procedures of the first linguistic test in Greek, designed specifically for brain mapping during awake craniotomies. The tasks are developed to comply with the special conditions and restrictions of language assessment inside the operating room. Each task is controlled for various psycholinguistic and lexical variables and it is associated with specific neuroanatomical areas and linguistic processes. Our population consists of 80 right-handed, healthy, Greek-speaking individuals aged 20-60 years. We found only a few main effects and interactions of demographic variables on our test scores. Most differences were found between age groups, since older participants tend to perform slightly worse than younger ones. Therefore, percentiles and cut-off scores were calculated separately for each demographic group. Regarding the clinical application of GLAABS, we describe the procedures we followed to administer it to brain tumor patients from our department and also discuss how sensitivity and specificity can affect patients' postoperative course.

Endogenous Melatonin Levels and Therapeutic Use of Exogenous Melatonin in Migraine: Systematic Review and Meta-Analysis.

BACKGROUND: Sleep disorders and circadian dysregulation appear to be associated with primary headache disorders. OBJECTIVE: The aim of this study was to review the existing evidence for the deployment of melatonin in migraine prophylaxis. Initially, case-control studies investigating nocturnal melatonin and 6-sulphatoxymelatonin (aMT6s, melatonin metabolite discarded by the urine) levels in patients with migraine and healthy controls (HC) would be reviewed and meta-analyzed. Second, results from randomized controlled trials (RCTs) and non-randomized studies evaluating the use of melatonin in migraine would be synthesized. METHODS: MEDLINE EMBASE, CENTRAL, PsycINFO, trial registries, Google Scholar, and OpenGrey were comprehensively searched. The quality of studies was assessed according to the Newcastle-Ottawa Scale (case-control studies) and the Risk-of-Bias Cochrane tool (RCTs). Random-effects (RE) or fixed-effects (FE) model was used based on heterogeneity among studies (homogeneity assumed when PQ > 0.1 and I2  < 30%). Publication bias was assessed by funnel plots. RESULTS: Literature search provided 11 case-control studies. Evidence was compatible with lower nocturnal serum [5 of 6 studies were synthesized due to deficient reporting of 1 abstract, migraine n = 197, HC n = 132, RE MD = -12.29 pg/ml, 95%CI = (-21.10, -3.49)] and urinary melatonin [3 studies, migraine n = 30, HC n = 29, RE MD = -0.12 nmol/nocturnal (12 hours) urinary collection, 95%CI = (-0.22, -0.03)], as well as urine aMT6s levels [1 study, migraine n = 146, HC n = 74, MD = -11.90 µg/nocturnal (12 hours) urine collection, 95%CI = (-19.23, -4.57)] in adult migraine patients compared to HC [1 study involving children did not reveal any difference regarding nocturnal urine aMT6s, n = 18 per group, MD = -6.00 µg/nocturnal (12 hours) urine collection, 95%CI = (-21.19, 9.19)]. Regarding the treatment-prevention of migraine, 7 RCTs and 9 non-randomized studies were retrieved. Data synthesis was not feasible for the comparison of melatonin and placebo due to the existing clinical and methodological heterogeneity of the 5 relevant RCTs. Overall, melatonin was more efficacious and equally safe with placebo in the prevention of migraine in adults (3 of 4 RCTs provided superior efficacy results for melatonin, 1 RCT revealed no difference regarding Headache Frequency -HF-), while there are limited data for children (1 RCT revealed no difference against placebo regarding HF). Additionally, no difference was revealed between melatonin and amitriptyline (1 RCT), sodium valproate (1 RCT) or propranolol (1 non-randomized study) with respect to their efficacy in adults with migraine, while melatonin was more effective than pizotifen (1 RCT). In children with migraine, amitriptyline is more efficacious regarding most assessed parameters (2 studies, n = 85 per group, HF: RE MD = 4.03, 95%CI = (2.64, 5.42), Headache Duration: RE MD = 0.72, 95%CI = (0.41, 1.03), Headache Severity: FE MD = 1.57, 95%CI = (1.13, 2.00), Response to Treatment: FE MD = 0.33, 95%CI = (0.16, 0.69), Headache Induced Disability Severity: RE MD = 6.07, 95%CI = (-11.87, 24.01 ), Analgesic Consumption - assessed in 1 study, n = 40 per group - MD = 1.11, 95%CI = (-0.10, 2.32)), although melatonin presents a superior safety profile than amitriptyline both in adults and in children. CONCLUSIONS: Melatonin may be of potential benefit in the treatment-prevention of migraine in adults, but complementary evidence from high-quality RCTs is required.

Serum Homocysteine, Pyridoxine, Folate, and Vitamin B12 Levels in Migraine: Systematic Review and Meta-Analysis.

BACKGROUND: Migraine, especially migraine with aura (MA), has been linked to increased risk for ischemic cerebrovascular disease. The possible role of elevated serum homocysteine (Hcy, a cause of thrombophilia) in migraine has been demonstrated by several studies. OBJECTIVE: The present study aims to review and meta-analyze data from studies investigating the difference of serum Hcy and Hcy lowering vitamins between migraine patients and healthy controls (HC), as well as between patients with MA and migraine without aura (MO). METHODS: Literature search involved MEDLINE, Embase, CENTRAL, Google Scholar, and trial registries. The Newcastle-Ottawa Scale was used to evaluate the quality of the retrieved studies. Standardized mean differences (SMDs) and 95% confidence intervals (95%CIs) were calculated. Funnel-plots were utilized for the evaluation of publication bias. RESULTS: Overall, 29 (28 case-control and 1 cross-sectional) studies were retrieved. Meta-analysis was indicative of higher Hcy concentration in migraine patients vs HC overall [adults and children: 16 studies, I2  = 81%, SMD = 0.41, 95%CI = (0.20, 0.61)]. Hcy was consistently elevated in adults with migraine [adults: 12 studies, I2  = 76%, SMD = 0.35, 95%CI = (0.15, 0.54); children: 1 study, SMD = 0.37, 95%CI = (-0.05, 0.79)]. Subgroup analyses reproduced the results for both adults with MA [7 studies, I2  = 83%, SMD = 0.37, 95%CI = (0.03, 0.71)] and MO [5 studies, I2  = 84%, SMD = 0.46, 95%CI = (0.03, 0.89)]. Figures for serum folate were lower in the overall comparison of migraine patients with HC [adults and children: 11 studies, I2  = 87%, SMD = -0.36, 95%CI = (-0.68, -0.05); adults: 8 studies, I2  = 6%, SMD = -0.11, 95%CI = (-0.22, 0.01); children: 1 study, SMD = -0.71, 95%CI = (-1.14, -0.29); MA adults: 4 studies, I2  = 44%, SMD = -0.16, 95%CI = (-0.35, 0.04); MO adults: 4 studies, I2  = 47%, SMD = -0.17, 95%CI = (-0.44, 0.10)]. Serum vitamin B12 levels were not different between migraine patients and HC [adults and children: 11 studies, I2  = 88%, SMD = -0.24, 95%CI = (-0.57, 0.09); adults: 8 studies, I2  = 57%, SMD = -0.10, 95%CI = (-0.28, 0.08); children: 1 study, SMD = 0.29, 95%CI = (-0.13, 0.71); MA adults: 4 studies, I2  = 63%, SMD = -0.14, 95%CI = (-0.48, 0.20); MO adults: 4 studies, I2  = 59%, SMD = -0.15, 95%CI = (-0.45, 0.15)]. Serum Hcy was lower in MO than MA [adults and children: 10 studies, I2  = 39%, SMD = 0.30, 95%CI = (0.14, 0.46), adults: 6 studies, I2  = 29%, SMD = 0.21, 95%CI = (0.09, 0.36), children: 1 study, SMD = 0.51, 95%CI = (0.22, 0.80)]. Serum folate and vitamin B12 did not differ between MA and MO. CONCLUSIONS: Our results suggest that there is a possible link between migraine, mainly MA, and elevated serum Hcy.

Pyridoxine, folate and cobalamin for migraine: A systematic review.

There is a possible relationship between migraine and hypercoagulability inducing factors, such as hyperhomocysteinemia. In this context, homocysteine (Hcy)-lowering vitamins (B6-folate-B12) may prove beneficial in the management-prophylaxis of migraine. We performed a systematic literature search in order to retrieve studies assessing the supplementation of B6, folate and B12 (alone or as adjunctive therapies) to migraine patients, as well as patients suffering from other primary headache disorders. MEDLINE, EMBASE, CENTRAL, Google Scholar, trial registries and OpenGrey were searched. Twelve relevant articles were retrieved. The management of acute migraine attacks with Hcy-lowering vitamins has not provided promising results (one randomized controlled trial-RCT-and one prospective uncontrolled trial). On the contrary, significant benefits were registered for the use of B6 alone, in combination with folate and in combination with folate and B12 in the prophylaxis of migraine with aura (MA) in adults compared to placebo (five RCTs, only one did not obtain significant results). Folate supplementation alone was not more efficacious than placebo (one RCT). Limited data for the prophylaxis of migraine without aura (MO) in children (two prospective uncontrolled trials) and adults (two prospective uncontrolled trials involving both MA and MO participants) impede the extraction of safe conclusions. An overall attractive safety profile was exhibited with gastrointestinal adverse events being the most common. Overall, a potential beneficial effect regarding the administration of B6, folate and/or B12 in the prophylaxis of MA in adults was indicated. Additional high-quality RCTs that will investigate MO in adults as well as MO and MA in children are warranted.