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Journal of Clinical Neuroscience :... Jun 2024Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of... (Review)
Review
BACKGROUND
Aneurysmal subarachnoid hemorrhage (aSAH) is a severe event often complicated by cerebral vasospasm (CV). This study aimed to assess the efficacy and safety of clazosentan, an endothelin receptor antagonist, in reducing CV, delayed cerebral ischemia (DCI), and the need for rescue therapy in aSAH patients, while evaluating its impact on functional outcomes and mortality.
METHODS
We conducted a literature search across multiple databases to identify relevant studies evaluating the effects of clazosentan in aSAH patients. Both cohort studies and randomized controlled trials (RCTs) were included. The primary outcomes were vasospasm incidence, moderate to severe vasospasm, DCI, and the need for rescue therapy. Secondary outcomes included functional outcomes, mortality, and adverse events. The data were pooled as Risk ratios (R/R) with 95 % confidence intervals (CI) using RevMan 5.4 software.
RESULTS
A total of 11 studies, including 10 published and one unpublished, comprising 8,469 patients were included in the meta-analysis. Clazosentan significantly reduced the incidence of vasospasm (R/R = 0.49: 0.34-0.70), moderate to severe vasospasm (R/R = 0.53: 0.46-0.61), DCI (R/R = 0.70: 0.59-0.82), and the need for rescue therapy (R/R = 0.65: 0.52-0.83) compared to placebo. However, no significant improvement in functional outcomes or mortality rates was observed. Clazosentan was associated with increased rates of pulmonary adverse events (R/R = 1.89: 1.64-2.18), hypotension (R/R = 2.47: 1.79-3.42), and anemia (R/R = 1.49: 1.23-1.79) but no increased risk of hepatobiliary adverse events or cerebral hemorrhage.
CONCLUSIONS
Clazosentan demonstrates efficacy in reducing vasospasm, moderate to severe vasospasm, DCI, and the need for rescue therapy in aSAH patients, but does not significantly improve functional outcomes or mortality rates. While associated with specific adverse events, clazosentan may be a valuable adjunctive therapy in the management of aSAH, particularly in a high-risk population for vasospasm.
PubMed: 38924824
DOI: 10.1016/j.jocn.2024.06.019 -
Acute and Critical Care May 2024This study evaluates the effectiveness of Therapeutic Hypothermia (TH) in treating poor-grade aneurysmal subarachnoid hemorrhage (SAH), focusing on functional outcomes,...
BACKGROUND
This study evaluates the effectiveness of Therapeutic Hypothermia (TH) in treating poor-grade aneurysmal subarachnoid hemorrhage (SAH), focusing on functional outcomes, mortality, and complications such as vasospasm, delayed cerebral ischemia (DCI), and hydrocephalus.
METHODS
Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, a comprehensive literature search was conducted across multiple databases, including Medline, Embase, and Cochrane Central, up to November 2023. Nine studies involving 368 patients were selected based on eligibility criteria focusing on TH in poor-grade SAH patients. Data extraction, bias assessment, and evidence certainty were systematically performed.
RESULTS
The primary analysis of unfavorable outcomes in 271 participants showed no significant difference between the TH and standard care groups (risk ratio [RR], 0.87). However, a significant reduction in vasospasm was observed in the TH group (RR, 0.63) among 174 participants. No significant differences were found in DCI, hydrocephalus, and mortality rates in the respective participant groups.
CONCLUSIONS
TH did not significantly improve primary unfavorable outcomes in poor-grade SAH patients. However, the reduction in vasospasm rates indicates potential specific benefits. The absence of significant findings in other secondary outcomes and mortality highlights the need for further research to better understand TH's role in treating this patient population.
PubMed: 38863359
DOI: 10.4266/acc.2024.00612 -
AJNR. American Journal of Neuroradiology May 2024Delayed cerebral ischemia and vasospasm are the most common causes of late morbidity following aneurysmal SAH, but their diagnosis remains challenging.
BACKGROUND
Delayed cerebral ischemia and vasospasm are the most common causes of late morbidity following aneurysmal SAH, but their diagnosis remains challenging.
PURPOSE
This systematic review and meta-analysis investigated the diagnostic performance of CTP for detection of delayed cerebral ischemia and vasospasm in the setting of aneurysmal SAH.
DATA SOURCES
Studies evaluating the diagnostic performance of CTP in the setting of aneurysmal SAH were searched on the Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Clinical Answers, Cochrane Methodology Register, Ovid MEDLINE, EMBASE, American College of Physicians Journal Club, Database of Abstracts of Reviews of Effects, Health Technology Assessment, National Health Service Economic Evaluation Database, PubMed, and Google Scholar from their inception to September 2023.
STUDY SELECTION
Thirty studies were included, encompassing 1786 patients with aneurysmal SAH and 2302 CTP studies. Studies were included if they compared the diagnostic accuracy of CTP with a reference standard (clinical or radiologic delayed cerebral ischemia, angiographic spasm) for the detection of delayed cerebral ischemia or vasospasm in patients with aneurysmal SAH. The primary outcome was accuracy for the detection of delayed cerebral ischemia or vasospasm.
DATA ANALYSIS
Bivariate random effects models were used to pool outcomes for sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Subgroup analyses for individual CTP parameters and early-versus-late study timing were performed. Bias and applicability were assessed using the modified QUADAS-2 tool.
DATA SYNTHESIS
For assessment of delayed cerebral ischemia, CTP demonstrated a pooled sensitivity of 82.1% (95% CI, 74.5%-87.8%), specificity of 79.6% (95% CI, 73.0%-84.9%), positive likelihood ratio of 4.01 (95% CI, 2.94-5.47), and negative likelihood ratio of 0.23 (95% CI, 0.12-0.33). For assessment of vasospasm, CTP showed a pooled sensitivity of 85.6% (95% CI, 74.2%-92.5%), specificity of 87.9% (95% CI, 79.2%-93.3%), positive likelihood ratio of 7.10 (95% CI, 3.87-13.04), and negative likelihood ratio of 0.16 (95% CI, 0.09-0.31).
LIMITATIONS
QUADAS-2 assessment identified 12 articles with low risk, 11 with moderate risk, and 7 with a high risk of bias.
CONCLUSIONS
For delayed cerebral ischemia, CTP had a sensitivity of >80%, specificity of >75%, and a low negative likelihood ratio of 0.23. CTP had better performance for the detection of vasospasm, with sensitivity and specificity of >85% and a low negative likelihood ratio of 0.16. Although the accuracy offers the potential for CTP to be used in limited clinical contexts, standardization of CTP techniques and high-quality randomized trials evaluating its impact are required.
PubMed: 38816018
DOI: 10.3174/ajnr.A8249 -
Therapeutic Hypothermia and Temperature... May 2024The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the... (Review)
Review
The effectiveness of target temperature management (TTM) in poor-grade aneurysmal subarachnoid hemorrhage (aSAH) remains a topic of debate. In order to assess the clinical efficacy of TTM in patients with poor-grade aSAH, we conducted a systematic review and meta-analysis. This research was registered in PROSPERO (CRD42023445582) and included all relevant publications up until October 2023. We compared the TTM groups with the control groups in terms of unfavorable outcomes (modified Rankin scale [mRS] score > 3), mortality, delayed cerebral ischemia (DCI), cerebral vasospasm (CVS), and specific complications. Subgroup analyses were performed based on country, study type, follow-up time, TTM method, cooling maintenance period, and rewarming rate. Effect sizes were calculated as relative risk (RR) using random-effect or fixed-effect models. The quality of the articles was assessed using the methodological index for non-randomized studies scale. Our analysis included a total of 5 clinical studies (including 1 randomized controlled trial) and 219 patients (85 in the TTM group and 134 in the control group). Most of the studies were of moderate quality. TTM was found to be associated with a statistically significant improvement in mortality (mRS score 6) rates compared with the control group (RR = 0.61, 95% confidence interval [CI]: 0.40-0.94, = 0.026). However, there was no statistically significant difference in unfavorable outcomes (mRS 4-6) between the TTM and control groups (RR = 0.94, 95% CI: 0.71-1.26, = 0.702). The incidence of adverse events, including DCI, CVS, pneumonia, cardiac complications, and electrolyte imbalance, did not significantly differ between the two groups. In conclusion, our overall results suggest that TTM does not significantly reduce unfavorable outcomes in poor-grade aSAH patients. However, TTM may decrease mortality rates. Preoperative TTM may cause patients to miss the opportunity for surgery, although it temporarily protects the brain. Furthermore, the incidence of adverse events was similar between the TTM and control groups.
PubMed: 38813648
DOI: 10.1089/ther.2024.0001 -
Journal of the Intensive Care Society May 2024Fragility analysis supplements the -value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we...
BACKGROUND
Fragility analysis supplements the -value and risk of bias assessment in the interpretation of results of randomised controlled trials. In this systematic review we determine the fragility index (FI) and fragility quotient (FQ) of randomised trials in aneurysmal subarachnoid haemorrhage.
METHODS
This is a systematic review registered with PROSPERO (ID: CRD42020173604). Randomised controlled trials in adults with aneurysmal subarachnoid haemorrhage were analysed if they reported a statistically significant primary outcome of mortality, function (e.g. modified Rankin Scale), vasospasm or delayed neurological deterioration.
RESULTS
We identified 4825 records with 18 randomised trials selected for analysis. The median fragility index was 2.5 (inter-quartile range 0.25-5) and the median fragility quotient was 0.015 (IQR 0.02-0.039). Five of 20 trial outcomes (25%) had a fragility index of 0. In seven trials (39.0%), the number of participants lost to follow-up was greater than or equal to the fragility index. Only 16.7% of trials are at low risk of bias.
CONCLUSION
Randomised controlled trial evidence supporting management of aneurysmal subarachnoid haemorrhage is weaker than indicated by conventional analysis using -values alone. Increased use of fragility analysis by clinicians and researchers could improve the translation of evidence to practice.
PubMed: 38737309
DOI: 10.1177/17511437231218199 -
Frontiers in Neurology 2024Cerebral vasospasm (CV) is a common complication of aneurysmal subarachnoid hemorrhage (aSAH), leading to increased morbidity and mortality rates. Endovascular therapy,...
BACKGROUND
Cerebral vasospasm (CV) is a common complication of aneurysmal subarachnoid hemorrhage (aSAH), leading to increased morbidity and mortality rates. Endovascular therapy, particularly intra-arterial vasodilator infusion (IAVI), has emerged as a potential alternative treatment for CV.
METHODS
A systematic review and meta-analysis were conducted to compare the efficacy of endovascular therapy with standard treatment in patients with CV following aSAH. The primary outcomes assessed were in-hospital mortality, discharge favorable outcome, and follow-up favorable outcome. Secondary outcomes included major infarction on CT, ICU stay duration, and total hospital stay.
RESULTS
Regarding our primary outcomes of interest, patients undergoing intervention exhibited a significantly lower in-hospital mortality compared to the standard treatment group, with the intervention group having only half the mortality risk (RR = 0.49, 95% CI [0.29, 0.83], = 0.008). However, there were no significant differences between the two groups in terms of discharge favorable outcome (RR = 0.99, 95% CI [0.68, 1.45], = 0.963) and follow-up favorable outcome (RR = 1.09, 95% CI [0.86, 1.39], = 0.485). Additionally, there was no significant difference in major infarction rates (RR = 0.79, 95% CI [0.34, 1.84], = 0.588). It is important to note that patients undergoing endovascular treatment experienced longer stays in the ICU (MD = 6.07, 95% CI [1.03, 11.12], = 0.018) and extended hospitalization (MD = 5.6, 95% CI [3.63, 7.56], < 0.001). Subgroup analyses based on the mode of endovascular treatment further supported the benefits of IAVI in lowering in-hospital mortality (RR = 0.5, 95% CI [0.27, 0.91], = 0.023).
CONCLUSION
Endovascular therapy, particularly IAVI, holds promising potential in reducing in-hospital mortality for patients with CV following aSAH. However, it did not show significant improvement in long-term prognosis and functional recovery. Further research with larger sample sizes and randomized controlled trials is necessary to validate these findings and optimize the treatment strategy for cerebral vasospasm in aSAH patients.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42023451741.
PubMed: 38715691
DOI: 10.3389/fneur.2024.1360511 -
Neurosurgical Review Apr 2024Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after... (Review)
Review
Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.
Topics: Humans; Subarachnoid Hemorrhage; DNA Methylation; Cerebral Infarction; Brain Ischemia; Biomarkers; Vasospasm, Intracranial; Cadherin Related Proteins
PubMed: 38594575
DOI: 10.1007/s10143-024-02381-5 -
CJC Open Feb 2024Myocardial infarction with nonobstructive coronary artery disease (MINOCA) is defined as acute myocardial infarction (AMI) with angiographically nonobstructive coronary... (Review)
Review
BACKGROUND
Myocardial infarction with nonobstructive coronary artery disease (MINOCA) is defined as acute myocardial infarction (AMI) with angiographically nonobstructive coronary artery disease. MINOCA represents 6% of all AMI cases and is associated with increased mortality and morbidity. However, the wide array of pathophysiological factors and causes associated with MINOCA presents a diagnostic conundrum. Therefore, we conducted a contemporary systematic review of the pathophysiology of MINOCA.
METHODS
A comprehensive systematic review of MINOCA was carried out through the utilization of the PubMed database. All systematic reviews, meta-analyses, randomized controlled trials, and cohort studies available in English or French that reported on the pathophysiology of MINOCA published after January 1, 2013 were retained.
RESULTS
Of the 600 identified records, 80 records were retained. Central to the concept of MINOCA is the definition of AMI, characterized by the presence of myocardial damage reflected by elevated cardiac biomarkers in the setting of acute myocardial ischemia. As a result, a structured approach should be adopted to thoroughly assess and address clinically overlooked obstructive coronary artery disease, and cardiac and extracardiac mechanisms of myocyte injury. Once these options have been ruled out, a diagnosis of MINOCA can be established, and the appropriate multimodal assessment can be conducted to determine its specific underlying cause (plaque disruption, epicardial coronary vasospasm, coronary microvascular dysfunction, and coronary embolism and/or spontaneous coronary dissection or supply-demand mismatch).
CONCLUSIONS
Integrating a suitable definition of AMI and understanding the pathophysiological mechanisms of MINOCA are crucial to ensure an effective multimodal diagnostic evaluation and the provision of adequate tailored therapies.
PubMed: 38487045
DOI: 10.1016/j.cjco.2023.11.014 -
European Journal of Neurology May 2024Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The... (Meta-Analysis)
Meta-Analysis
Frequency of ischaemic stroke and intracranial haemorrhage in patients with reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) - A systematic review.
BACKGROUND
Posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS) may cause ischaemic stroke and intracranial haemorrhage. The aim of our study was to assess the frequency of the afore-mentioned outcomes.
METHODS
We performed a PROSPERO-registered (CRD42022355704) systematic review and meta-analysis accessing PubMed until 7 November 2022. The inclusion criteria were: (1) original publication, (2) adult patients (≥18 years), (3) enrolling patients with PRES and/or RCVS, (4) English language and (5) outcome information. Outcomes were frequency of (1) ischaemic stroke and (2) intracranial haemorrhage, divided into subarachnoid haemorrhage (SAH) and intraparenchymal haemorrhage (IPH). The Cochrane Risk of Bias tool was used.
RESULTS
We identified 848 studies and included 48 relevant studies after reviewing titles, abstracts and full text. We found 11 studies on RCVS (unselected patients), reporting on 2746 patients. Among the patients analysed, 15.9% (95% CI 9.6%-23.4%) had ischaemic stroke and 22.1% (95% CI 10%-39.6%) had intracranial haemorrhage. A further 20.3% (95% CI 11.2%-31.2%) had SAH and 6.7% (95% CI 3.6%-10.7%) had IPH. Furthermore, we found 28 studies on PRES (unselected patients), reporting on 1385 patients. Among the patients analysed, 11.2% (95% CI 7.9%-15%) had ischaemic stroke and 16.1% (95% CI 12.3%-20.3%) had intracranial haemorrhage. Further, 7% (95% CI 4.7%-9.9%) had SAH and 9.7% (95% CI 5.4%-15%) had IPH.
CONCLUSIONS
Intracranial haemorrhage and ischaemic stroke are common outcomes in PRES and RCVS. The frequency reported in the individual studies varied considerably.
Topics: Adult; Humans; Brain Ischemia; Stroke; Posterior Leukoencephalopathy Syndrome; Vasoconstriction; Vasospasm, Intracranial; Intracranial Hemorrhages; Ischemic Stroke; Subarachnoid Hemorrhage
PubMed: 38470001
DOI: 10.1111/ene.16246 -
PloS One 2024Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches and reversible vasoconstriction of the cerebral arteries on... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Reversible cerebral vasoconstriction syndrome (RCVS) is a syndrome of recurrent thunderclap headaches and reversible vasoconstriction of the cerebral arteries on neuroimaging within 3 months of onset. Initial non-contrast computed tomography (CT) can reveal abnormalities such as ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage (SAH) can be present in patients with RCVS and may delay diagnosis.
AIMS
We conducted a systematic review and meta-analysis in accordance with the PRISMA guidelines. We aimed to estimate the prevalence of imaging abnormalities on initial non-contrast CT head in adult patients with RCVS.
DATA SOURCES & ELIGIBILITY CRITERIA
We searched electronic databases including MEDLINE, EMBASE, and the Cochrane Register of Clinical Trials from inception to August 2, 2022. Eligible studies included articles reporting the prevalence of non-contrast CT abnormalities on initial neuroimaging in patients with RCVS, aged 18 and older. Case series, observational studies and clinical trials were included. Data was extracted directly from included papers using a standardized data charting form.
RESULTS
The search yielded 722 titles with duplicates removed. Twenty studies that included 379 patients with RCVS met inclusion criteria. We classified non-contrast CT abnormalities as either ischemic stroke, ICH, or SAH. We pooled prevalence data using a random effects model with the inverse-variance weighted method. The most common imaging finding was SAH with a pooled prevalence of 24% (95% CI:17%-33%), followed by ICH at 14% (95% CI:8%-22%), and ischemic stroke at 10% (95% CI:7%-14%). The pooled prevalence of any of these imaging abnormalities on initial non-contrast CT was 31% (95% CI:23%-40%). Risk of bias was moderate to very-high-risk for case-series and low-risk for observational studies.
CONCLUSION
Our review demonstrates that one-third of patients with RCVS will have an abnormality on initial non-contrast CT head, including either an ischemic stroke, ICH, or SAH. These findings highlight the diagnostic challenges of RCVS imaging and contribute to our understanding of this disease.
Topics: Adult; Humans; Vasoconstriction; Prevalence; Vasospasm, Intracranial; Cerebrovascular Disorders; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Headache; Ischemic Stroke
PubMed: 38466700
DOI: 10.1371/journal.pone.0295558