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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 -
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 -
Annals of Medicine and Surgery (2012) Mar 2024This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of...
Reversible cerebral vasoconstriction syndrome and posterior reversible encephalopathy syndrome following vaccination: analysis of the VAERS database and systematic review.
OBJECTIVES
This study aimed to analyze the Vaccine Adverse Event Reporting System (VAERS) database and systematically review the literature to provide a comprehensive analysis of reversible cerebral vasoconstriction syndrome (RCVS) and posterior reversible encephalopathy syndrome (PRES) secondary to vaccination.
METHODS
The authors analyzed the VAERS database and conducted a systematic review following PRISMA guidelines. The inclusion criteria for VAERS data were a score of ≥3 on the RCVS score and/or radiographic findings consistent with the diagnosis of RCVS or PRES. The systematic review was registered with PROSPERO.
RESULTS
Our combined data set included 29 cases (9 RCVS and 20 PRES). Most cases were women (72.4%) with a mean age of 50.7 years (SD 19.4 years). Most cases were associated with COVID-19 mRNA vaccines (58.6% Moderna, 20.7% Pfizer). Hypertension (37.9%), hyperlipidemia (13.7%), chronic kidney disease (CKD) (10.3%), and end-stage renal disease (6.8%) were common comorbidities. Furthermore, 20.6% (6/29) of cases were on immunosuppression therapy for various reasons. The mean time to symptom onset was 10.49 days after vaccination (SD 18.60), and the mean duration of hospitalization was 7.42 days (SD 5.94). The symptoms reported the most frequently were headache (41.3%), elevated blood pressure (31.0%), and emesis (17.2%). Typical radiographic findings included T2/FLAIR hyperintensities affecting the parieto-occipital lobes, indicative of vasogenic and/or cytotoxic edema.
CONCLUSIONS
This study provides a comprehensive analysis of postvaccine RCVS and PRES. Both disease states were seen most often in those with pre-existing risk factors such as female sex, age over 50, hypertension, renal disease, and immunosuppression. Vaccines and their associated immune response may cause endothelial dysfunction leading to cerebral vasospasm and loss of cerebral autoregulation. However, further research is required to understand the underlying pathophysiological mechanisms. Despite the associations found, the absolute risk of these syndromes remains extremely low compared to the immense benefits of vaccination.
PubMed: 38463101
DOI: 10.1097/MS9.0000000000001407 -
Journal of the American Heart... Mar 2024Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have...
BACKGROUND
Delayed cerebral ischemia represents a significant contributor to death and disability following aneurysmal subarachnoid hemorrhage. Although preclinical models have shown promising results, clinical trials have consistently failed to replicate the success of therapeutic strategies. The lack of standardized experimental setups and outcome assessments, particularly regarding secondary vasospastic/ischemic events, may be partly responsible for the translational failure. The study aims to delineate the procedural characteristics and assessment modalities of secondary vasospastic and ischemic events, serving as surrogates for clinically relevant delayed cerebral ischemia, in recent rat and murine subarachnoid hemorrhage models.
METHODS AND RESULTS
We conducted a systematic review of rat and murine in vivo subarachnoid hemorrhage studies (published: 2016-2020) using delayed cerebral ischemia/vasospasm as outcome parameters. Our analysis included 102 eligible studies. In murine studies (n=30), the endovascular perforation model was predominantly used, while rat studies primarily employed intracisternal blood injection to mimic subarachnoid hemorrhage. Particularly, the injection models exhibited considerable variation in injection volume, rate, and cerebrospinal fluid withdrawal. Peri-interventional monitoring was generally inadequately reported across all models, with body temperature and blood pressure being the most frequently documented parameters (62% and 34%, respectively). Vasospastic events were mainly assessed through microscopy of large cerebral arteries. In 90% of the rat and 86% of the murine studies, only male animals were used.
CONCLUSIONS
Our study underscores the substantial heterogeneity in procedural characteristics and outcome assessments of experimental subarachnoid hemorrhage research. To address these challenges, drafting guidelines for standardization and ensuring rigorous control of methodological and experimental quality by funders and journals are essential.
REGISTRATION
URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42022337279.
Topics: Animals; Male; Mice; Rats; Blood Pressure; Brain Ischemia; Cerebral Infarction; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 38420758
DOI: 10.1161/JAHA.123.032694 -
Journal of Neurosciences in Rural... 2023This study reviews the effect of albumin-induced volume expansion therapy on symptomatic vasospasm and clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH). (Review)
Review
OBJECTIVES
This study reviews the effect of albumin-induced volume expansion therapy on symptomatic vasospasm and clinical outcome in aneurysmal subarachnoid hemorrhage (aSAH).
MATERIALS AND METHODS
Computer searches carried out from the Scopus, Medline, Embase, Web of Science, the Cochrane Library, and Internet documents; hand searching of medical journals; and review of reference lists. Randomized controlled trials (RCT) and observational studies (OSs) comparing albumin therapy in combination or alone with crystalloid therapy for the treatment of cerebral vasospasm in aSAH were included in the study. Risk-of-bias assessment was conducted using ROB2.0 and ROBINS-I tools for RCTs and Oss, respectively.
RESULTS
Out of a total of 1078 searches, one RCT (published in two articles) and one observational (retrospective) study were included for final analysis. In RCT, albumin was used for volume expansion therapy with a baseline crystalloid regime and comparison made between hypervolemic and normovolemic groups and it showed no beneficial effects on symptomatic vasospasm and clinical outcomes based on the Glasgow outcome scale. Furthermore, the use of albumin showed a tendency for sodium retention with lowering of glomerular filtration rate, limiting the amount of total fluid required for targeted central venous pressure values, and thereby avoiding fluid overload manifestations. The retrospective study results between albumin versus non-albumin groups (crystalloids only) supported improved outcomes in the former group with lower in-hospital mortality. Cardiorespiratory complications were equivocal in RCT and increased in non-albumin group in the retrospective study. Risk-of-bias assessment analyses revealed "some concerns" in RCT and "serious" limitation in OS due to its retrospective design.
CONCLUSION
Albumin-induced volume expansion therapy for cerebral vasospasm does not have substantiative evidence to improve cerebral vasospasm and clinical outcomes in aSAH. Studies with well-designed RCTs are required to compare the use of albumin for volume expansion therapy versus standard fluid management using crystalloids to mitigate the scarcity of published data.
PubMed: 38059246
DOI: 10.25259/JNRP_372_2023