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Critical Care (London, England) Aug 2021Acute brain injuries are associated with high mortality rates and poor long-term functional outcomes. Measurement of cerebrospinal fluid (CSF) biomarkers in patients...
BACKGROUND
Acute brain injuries are associated with high mortality rates and poor long-term functional outcomes. Measurement of cerebrospinal fluid (CSF) biomarkers in patients with acute brain injuries may help elucidate some of the pathophysiological pathways involved in the prognosis of these patients.
METHODS
We performed a systematic search and descriptive review using the MEDLINE database and the PubMed interface from inception up to June 29, 2021, to retrieve observational studies in which the relationship between CSF concentrations of protein biomarkers and neurological outcomes was reported in patients with acute brain injury [traumatic brain injury, subarachnoid hemorrhage, acute ischemic stroke, status epilepticus or post-cardiac arrest]. We classified the studies according to whether or not biomarker concentrations were associated with neurological outcomes. The methodological quality of the studies was evaluated using the Newcastle-Ottawa quality assessment scale.
RESULTS
Of the 39 studies that met our criteria, 30 reported that the biomarker concentration was associated with neurological outcome and 9 reported no association. In TBI, increased extracellular concentrations of biomarkers related to neuronal cytoskeletal disruption, apoptosis and inflammation were associated with the severity of acute brain injury, early mortality and worse long-term functional outcome. Reduced concentrations of protein biomarkers related to impaired redox function were associated with increased risk of neurological deficit. In non-traumatic acute brain injury, concentrations of CSF protein biomarkers related to dysregulated inflammation and apoptosis were associated with a greater risk of vasospasm and a larger volume of brain ischemia. There was a high risk of bias across the studies.
CONCLUSION
In patients with acute brain injury, altered CSF concentrations of protein biomarkers related to cytoskeletal damage, inflammation, apoptosis and oxidative stress may be predictive of worse neurological outcomes.
Topics: Adult; Biomarkers; Brain Injuries; Cerebrospinal Fluid; Humans; Prognosis; Proteins
PubMed: 34353354
DOI: 10.1186/s13054-021-03698-z -
BMJ Open Jul 2021The use of aspirin to prevent cardiovascular disease in vasospastic angina (VSA) patients without significant stenosis has yet to be investigated. This study aimed to... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
The use of aspirin to prevent cardiovascular disease in vasospastic angina (VSA) patients without significant stenosis has yet to be investigated. This study aimed to investigate the efficacy of aspirin use among VSA patients.
DESIGN
Systematic review and meta-analysis.
DATA SOURCES
PubMed, Web of Science and Cochrane Central Register of Controlled Trials were searched for relevant information prior to October 2020.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Aspirin use versus no aspirin use (placebo or no treatment) among VSA patients without significant stenosis.
DATA EXTRACTION AND SYNTHESIS
Two investigators extracted the study data. ORs and 95% CIs were calculated and graphed as forest plots. The Newcastle-Ottawa Quality Assessment Scale tool and Begg's funnel plot were used to assess risk of bias.
RESULTS
Four propensity-matched cohorts, one retrospective analysis and one prospective multicentre cohort, in total comprising 3661 patients (aspirin use group, n=1695; no aspirin use group, n=1966) were included in this meta-analysis. Aspirin use and the incidence of major cardiovascular adverse events with follow-up of 1-5 years were not significantly correlated (combined OR=0.90, 95% CI: 0.55 to 1.68, p=0.829, I=82.2%; subgroup analysis: OR=1.09, 95% CI: 0.81 to 1.47, I=0%). No significant difference was found between aspirin use and the incidence of myocardial infarction (OR=0.62, 95% CI: 0.09 to 4.36, p=0.615, I=73.8%) or cardiac death (OR=1.73, 95% CI: 0.61 to 4.94, p=0.444, I=0%) during follow-up.
CONCLUSION
Aspirin use may not reduce the risk of future cardiovascular events in VSA patients without significant stenosis.
PROSPERO REGISTRATION NUMBER
CRD42020214891.
Topics: Aspirin; Coronary Vasospasm; Humans; Myocardial Infarction; Prospective Studies; Retrospective Studies
PubMed: 34326051
DOI: 10.1136/bmjopen-2021-048719 -
Frontiers in Neurology 2021The efficacy of statin-treatment in aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We aimed to investigate the effects of statin-treatment in...
The efficacy of statin-treatment in aneurysmal subarachnoid hemorrhage (SAH) remains controversial. We aimed to investigate the effects of statin-treatment in non-aneurysmal (na)SAH in accordance with animal research data illustrating the pathophysiology of naSAH. We systematically searched PubMed using PRISMA-guidelines and selected experimental studies assessing the statin-effect on SAH. Detecting the accordance of the applied experimental models with the pathophysiology of naSAH, we analyzed our institutional database of naSAH patients between 1999 and 2018, regarding the effect of statin treatment in these patients and creating a translational concept. Patient characteristics such as statin-treatment (simvastatin 40 mg/d), the occurrence of cerebral vasospasm (CVS), delayed infarction (DI), delayed cerebral ischemia (DCI), and clinical outcome were recorded. In our systematic review of experimental studies, we found 13 studies among 18 titles using blood-injection-animal-models to assess the statin-effect in accordance with the pathophysiology of naSAH. All selected studies differ on study-setting concerning drug-administration, evaluation methods, and neurological tests. Patients from the Back to Bedside project, including 293 naSAH-patients and 51 patients with simvastatin-treatment, were recruited for this analysis. Patients under treatment were affected by a significantly lower risk of CVS ( < 0.01; OR 3.7), DI ( < 0.05; OR 2.6), and DCI ( < 0.05; OR 3). Furthermore, there was a significant association between simvastatin-treatment and favorable-outcome ( < 0.05; OR 3). However, dividing patients with statin-treatment in pre-SAH ( = 31) and post-SAH ( = 20) treatment groups, we only detected a tenuously significant higher chance for a favorable outcome ( < 0.05; OR 0.05) in the small group of 20 patients with statin post-SAH treatment. Using a multivariate-analysis, we detected female gender (55%; < 0.001; OR 4.9), Hunt&Hess ≤III at admission ( < 0.002; OR 4), no anticoagulant-therapy ( < 0.0001; OR 0.16), and statin-treatment ( < 0.0001; OR 24.2) as the main factors improving the clinical outcome. In conclusion, we detected a significantly lower risk for CVS, DCI, and DI in naSAH patients under statin treatment. Additionally, a significant association between statin treatment and favorable outcome 6 months after naSAH onset could be confirmed. Nevertheless, unified animal experiments should be considered to create the basis for developing new therapeutic schemes.
PubMed: 34054685
DOI: 10.3389/fneur.2021.620096 -
Journal of Epilepsy Research Dec 2020Seizures in aneurysmal subarachnoid haemorrhage (aSAH) have been described secondary to SAH, changes in cortical function, vasospasm and as a result of treatment... (Review)
Review
Seizures in aneurysmal subarachnoid haemorrhage (aSAH) have been described secondary to SAH, changes in cortical function, vasospasm and as a result of treatment effects. Seizures are one of the important clinical determinants in neurological outcome of aSAH. Various studies support the notion of less risk of future seizures in endovascular treatment as compared to the microsurgical clipping, yet there is no conclusive evidence in favour or against the seizure occurrence in aSAH patients after endovascular treatment as compared to the microsurgical treatment. To carry out a systematic review and meta-analysis of the risk of seizures after endovascular management (coiling) of ruptured intracranial aneurysms. A literature search was performed in electronic database of PubMed, MEDLINE, Embase, and Scopus from inception to February 2020, using the terms Seizure, Intracranial aneurysms, embolization, with no constraints applied. Data were pooled using a random-effect model, results were abstracted as odds ratios (ORs) and 95% confidence interval (CI), and heterogeneity was reported as Chi-square. Five studies involving 3,077 patients were included in the meta-analysis. After endovascular management of aSAH, seizure risk was increased by a worse clinical severity (World Federation of Neurosurgery scale or Hunt and Hess) (OR, 3.34; 95% CI, 2.69-4.16; <0.00001), severe vasospasm (OR, 2.20; 95% CI, 1.67-2.92; <0.00001), cerebral infarction (OR, 5.19; 95% CI, 3.23-8.35; <0.00001), and cerebral edema (OR, 1.79; 95% CI, 1.37-2.34; <0.0000). Worse clinical severity, vasospasm, cerebral infarction and cerebral oedema are significant risk factors for the development of seizures after endovascular intervention in aSAH. The mechanism for this correlation is not clear.
PubMed: 33659196
DOI: 10.14581/jer.20009 -
AJNR. American Journal of Neuroradiology Mar 2021Conventional angiography is the benchmark examination to diagnose cerebral vasospasm, but there is limited evidence regarding its reliability. Our goals were the...
BACKGROUND AND PURPOSE
Conventional angiography is the benchmark examination to diagnose cerebral vasospasm, but there is limited evidence regarding its reliability. Our goals were the following: 1) to systematically review the literature on the reliability of the diagnosis of cerebral vasospasm using conventional angiography, and 2) to perform an agreement study among clinicians who perform endovascular treatment.
MATERIALS AND METHODS
Articles reporting a classification system on the degree of cerebral vasospasm on conventional angiography were systematically searched, and agreement studies were identified. We assembled a portfolio of 221 cases of patients with subarachnoid hemorrhage and asked 17 raters with different backgrounds (radiology, neurosurgery, or neurology) and experience (junior ≤10 and senior >10 years) to independently evaluate cerebral vasospasm in 7 vessel segments using a 3-point scale and to evaluate, for each case, whether findings would justify endovascular treatment. Nine raters took part in the intraobserver reliability study.
RESULTS
The systematic review showed a very heterogeneous literature, with 140 studies using 60 different nomenclatures and 21 different thresholds to define cerebral vasospasm, and 5 interobserver studies reporting a wide range of reliability (κ = 0.14-0.87). In our study, only senior raters reached substantial agreement (κ ≥ 0.6) on vasospasm of the supraclinoid ICA, M1, and basilar segments and only when assessments were dichotomized (presence or absence of ≥50% narrowing). Agreement on whether to proceed with endovascular management of vasospasm was only fair (κ ≤ 0.4).
CONCLUSIONS
Research on cerebral vasospasm would benefit from standardization of definitions and thresholds. Dichotomized decisions by experienced readers are required for the reliable angiographic diagnosis of cerebral vasospasm.
Topics: Adolescent; Adult; Aged; Catheters; Cerebral Angiography; Female; Humans; Male; Middle Aged; Observer Variation; Reproducibility of Results; Subarachnoid Hemorrhage; Vasospasm, Intracranial; Young Adult
PubMed: 33509923
DOI: 10.3174/ajnr.A7021 -
Revista Brasileira de Terapia Intensiva 2020To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage.
OBJECTIVE
To systematically review the current evidence on the efficacy of milrinone in the treatment of cerebral vasospasm after subarachnoid hemorrhage.
METHODS
The Pubmed®, Cochrane and Embase databases were screened for articles published from April 2001 to February 2019. Two independent reviewers performed the methodological quality screening and data extraction of the studies.
RESULTS
Twenty-two studies were found to be relevant, and only one of these was a randomized control trial. Studies showed marked heterogeneity and weaknesses in key methodological criteria. Most patients presented with moderate to severe vasospasm. Angiography was the main method of diagnosing vasospasm. Intra-arterial administration of milrinone was performed in three studies, intravenous administration was performed in nine studies, and both routes of administration in six studies; the intrathecal route was used in two studies, the cisternal route in one study and endovascular administration in one study. The side effects of milrinone were described in six studies. Twenty-one studies indicated resolution of vasospasm.
CONCLUSION
The current evidence indicates that milrinone may have a role in treatment of vasospasm after aneurysmal subarachnoid hemorrhage. However, only one randomized control trial was performed, with a low quality level. Our findings indicate the need for future randomized control trials with patient-centered outcomes to provide definitive recommendations.
Topics: Humans; Infusions, Intravenous; Milrinone; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Vasodilator Agents; Vasospasm, Intracranial
PubMed: 33470361
DOI: 10.5935/0103-507X.20200097 -
Cureus May 2020Cerebral vasospasm is a rare life-threatening complication of transsphenoidal surgery (TSS). We report our experience with two cases of symptomatic vasospasm after... (Review)
Review
Cerebral vasospasm is a rare life-threatening complication of transsphenoidal surgery (TSS). We report our experience with two cases of symptomatic vasospasm after endoscopic TSS, alongside a systematic review of published cases. Two patients who underwent endoscopic TSS for resection of a tuberculum sella meningioma (case 1) and pituitary adenoma (case 2) developed symptomatic vasospasm. Clinical variables, including demographics, histopathology, the extent of subarachnoid hemorrhage (SAH), diabetes insipidus (DI), day of vasospasm, vasospasm symptoms, vessels involved, management, and clinical outcome, were retrospectively extracted. We subsequently reviewed published cases of symptomatic post-TSS vasospasm. Including our two cases, we identified 34 reported cases of TSS complicated by symptomatic vasospasm. Female patients accounted for 20 (58.8%) of 34 cases. The average age was 48.1 ± 12.9 years. The majority of patients exhibited postoperative SAH (70.6%). The average delay to vasospasm presentation was 8.5 ± 3.6 days. The majority of patients exhibited vasospasm in multiple vessels, typically involving the anterior circulation. Hemodynamic augmentation with hemodilution, hypertension, and hypervolemia was the most common treatment. Death occurred in six (17.6%) of 34 patients. Common deficits included residual extremity weakness (17.6%), pituitary insufficiency (8.8%), and cognitive deficits (8.8%). Symptomatic vasospasm is a rare, potentially fatal complication of TSS. The most consistent risk factor is SAH. Early diagnosis requires a high index of suspicion when confronted with intractable DI, acute mental status change, or focal deficits in the days after TSS. Morbidity and death are significant risks in patients with this complication.
PubMed: 32566415
DOI: 10.7759/cureus.8171 -
Journal of Clinical Neuroscience :... Aug 2020Data regarding the efficacy and safety of smoking-cessation pharmacotherapy after stroke are lacking. We systematically reviewed data on this topic by searching Medline,...
Data regarding the efficacy and safety of smoking-cessation pharmacotherapy after stroke are lacking. We systematically reviewed data on this topic by searching Medline, Cochrane, and Clinicaltrials.gov to identify randomized clinical trials (RCT) and observational studies that assessed the efficacy and safety of nicotine replacement therapy (NRT), varenicline, and bupropion in patients with stroke and TIA. We included studies that reported rates of smoking cessation, worsening or recurrent cerebrovascular disease, seizures, or neuropsychiatric events. We identified 2 RCTs and 6 observational studies; 3 included ischemic stroke and TIA, 2 subarachnoid hemorrhage (SAH), and 3 did not specify. Four studies assessed efficacy; cessation rates ranged from 33% to 66% with pharmacological therapy combined with behavioral interventions versus 15% to 46% without, but no individual study demonstrated a statistically significant benefit. Safety data for varenicline and buopropion in ischemic stroke were scarce. Patients with SAH who received NRT had more seizures (9% vs 2%; P = 0.024) and delirium (19% vs 7%; P = 0.006) in one study, but less frequent vasospasm in 3 studies. In conclusion, combined with behavioral interventions, smoking-cessation therapies resulted in numerically higher cessation rates. Limited safety data may prompt caution regarding seizures and delirium in patients with subarachnoid hemorrhage.
Topics: Bupropion; Female; Humans; Ischemic Attack, Transient; Observational Studies as Topic; Randomized Controlled Trials as Topic; Seizures; Smoking; Smoking Cessation; Stroke; Tobacco Use Cessation Devices; Varenicline
PubMed: 32334957
DOI: 10.1016/j.jocn.2020.04.026 -
International Journal of Molecular... Apr 2020Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Neurosurgical clipping or endovascular coiling can successfully obliterate...
Aneurysmal subarachnoid hemorrhage (aSAH) is a complex and potentially deadly disease. Neurosurgical clipping or endovascular coiling can successfully obliterate ruptured aneurysms in almost every case. However, despite successful interventions, the clinical outcomes of aSAH patients are often poor. The reasons for poor outcomes are numerous, including cerebral vasospasm (CVS), post-hemorrhagic hydrocephalus, systemic infections and delayed cerebral ischemia. Although CVS with subsequent cerebral ischemia is one of the main contributors to brain damage after aSAH, little is known about the underlying molecular mechanisms of brain damage. This review emphasizes the importance of pharmacological interventions targeting high mobility group box 1 (HMGB1)-mediated brain damage after subarachnoid hemorrhage (SAH) and CVS. We searched Pubmed, Ovid medline and Scopus for "subarachnoid hemorrhage" in combination with "HMGB1". Based on these criteria, a total of 31 articles were retrieved. After excluding duplicates and selecting the relevant references from the retrieved articles, eight publications were selected for the review of the pharmacological interventions targeting HMGB1 in SAH. Damaged central nervous system cells release damage-associated molecular pattern molecules (DAMPs) that are important for initiating, driving and sustaining the inflammatory response following an aSAH. The discussed evidence suggested that HMGB1, an important DAMP, contributes to brain damage during early brain injury and also to the development of CVS during the late phase. Different pharmacological interventions employing natural compounds with HMGB1-antagonizing activity, antibody targeting of HMGB1 or scavenging HMGB1 by soluble receptors for advanced glycation end products (sRAGE), have been shown to dampen the inflammation mediated brain damage and protect against CVS. The experimental data suggest that HMGB1 inhibition is a promising strategy to reduce aSAH-related brain damage and CVS. Clinical studies are needed to validate these findings that may lead to the development of potential treatment options that are much needed in aSAH.
Topics: Animals; Antibodies, Monoclonal; Biomarkers; Disease Management; Disease Susceptibility; HMGB1 Protein; Humans; Molecular Targeted Therapy; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 32295146
DOI: 10.3390/ijms21082709 -
AJNR. American Journal of Neuroradiology Apr 2020Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited...
BACKGROUND AND PURPOSE
Computed tomography angiography offers a non-invasive alternative to DSA for the assessment of cerebral vasospasm following subarachnoid hemorrhage but there is limited evidence regarding its reliability. Our aim was to perform a systematic review (Part I) and to assess (Part II) the inter- and intraobserver reliability of CTA in the diagnosis of cerebral vasospasm.
MATERIALS AND METHODS
In Part I, articles reporting the reliability of CTA up to May 2018 were systematically searched and evaluated. In Part II, 11 raters independently graded 17 arterial segments in each of 50 patients with SAH for the presence of vasospasm using a 4-category scale. Raters were additionally asked to judge the presence of any moderate/severe vasospasm (≥ 50% narrowing) and whether findings would justify augmentation of medical treatment or conventional angiography ± balloon angioplasty. Four raters took part in the intraobserver reliability study.
RESULTS
In Part I, the systematic review revealed few studies with heterogeneous vasospasm definitions. In Part II, we found interrater reliability to be moderate at best (κ ≤ 0.6), even when results were stratified according to specialty and experience. Intrarater reliability was substantial (κ > 0.6) in 3/4 readers. In the per arterial segment analysis, substantial agreement was reached only for the middle cerebral arteries, and only when senior raters' judgments were dichotomized (presence or absence of ≥50% narrowing). Agreement on the medical or angiographic management of vasospasm based on CTA alone was less than substantial (κ ≤ 0.6).
CONCLUSIONS
The diagnosis of vasospasm using CTA alone was not sufficiently repeatable among observers to support its general use to guide decisions in the clinical management of patients with SAH.
Topics: Cerebral Angiography; Computed Tomography Angiography; Female; Humans; Male; Middle Aged; Observer Variation; Reproducibility of Results; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 32217551
DOI: 10.3174/ajnr.A6462