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World Neurosurgery Mar 2024Cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH) continues to be a major source of morbidity despite significant clinical and basic science... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage (aSAH) continues to be a major source of morbidity despite significant clinical and basic science research. The removal of blood and its degradation products from the subarachnoid space through prophylactic lumbar drainage (LD) is a favorable option. However, several studies have delivered conflicting conclusions on its efficacy after aSAH.
METHODS
Systematic searches of Medline, Embase, and Cochrane Central Register of Controlled Trials were performed. The primary outcome was a good functional outcome (modified Rankin scale score, 0-2). Secondary outcomes included symptomatic vasospasm, secondary cerebral infarction, and mortality.
RESULTS
A total of 14 studies reporting on 2473 patients with aSAH were included in the meta-analysis. Compared with the non-LD group, no significant differences were found in the rates of good functional outcomes in the LD group at discharge to 1 month (risk ratio [RR], 1.28; 95% confidence interval [CI], 0.64-2.58) or at 6 months (RR, 1.12; 95% CI, 0.97-1.41). These findings were consistent in the subgroup analyses of only randomized controlled trials or observational studies. LD was associated with lower rates of symptomatic vasospasm (RR, 0.61; 95% CI, 0.48-0.77), secondary cerebral infarction (RR, 0.59; 95% CI, 0.45-0.79), and mortality at discharge to 1 month (RR, 0.58; 95% CI, 0.41-0.82). The effect on mortality diminished at 6 months (RR, 0.70; 95% CI, 0.34-1.45). However, when analyzing only randomized controlled trials, the benefit of LD on lower rates of mortality continued even at 6 months (RR, 0.75; 95% CI, 0.58-0.99).
CONCLUSIONS
For aSAH patients, the use of LD is associated with benefits in the rates of vasospasm, secondary cerebral infarctions, and mortality, without an increased risk of adverse events.
Topics: Humans; Autonomic Nervous System Diseases; Cerebral Infarction; Cerebrospinal Fluid Leak; Drainage; Subarachnoid Hemorrhage; Subarachnoid Space; Treatment Outcome; Vasospasm, Intracranial
PubMed: 38246528
DOI: 10.1016/j.wneu.2024.01.062 -
Journal of Clinical Neuroscience :... Nov 2022Vasospasm is a common complication following subarachnoid hemorrhage (SAH), causing increased ischemia and tissue injury, and is implicated as a major risk factor for... (Review)
Review
INTRODUCTION
Vasospasm is a common complication following subarachnoid hemorrhage (SAH), causing increased ischemia and tissue injury, and is implicated as a major risk factor for poor outcomes. The success of current treatments for vasospasm is limited, with limited efficacy and unclear clinical benefits. Exosomes, vesicles that carry small molecules such as miRNA, have been theorized as a potential vasospasm treatment. In this study, we aim to survey the current literature discussing the role of exosomes in the setting of SAH.
METHODS
Following PRISMA guidelines, we performed a scoping review evaluating the role of exosomes in the treatment of SAH. The search was conducted using PubMed and Scopus, and all original research papers studying exosomal profiles of SAH research subjects or SAH therapy were eligible for inclusion.
RESULTS
After screening and full text review, seven papers were selected for final inclusion. Of these, two studies analyzed the expression profile of endogenous exosomes after SAH. Four papers identified and characterized miRNA-based exosomal therapies to attenuate early brain injury (EBI) after SAH. One paper discussed the role of protein overexpression in exosome delivery of miRNA for EBI after SAH. Interestingly, all identified papers studying exosomal therapy demonstrated anti-apoptotic or anti-inflammatory effects of miRNA exosomes acting via the BDNF/TrkB/CREB or HDAC3/NF-κB pathways.
CONCLUSION
Identified studies demonstrate potential neuroprotective benefits of miRNA-based exosomal treatment of EBI and SAH. Findings warrant further research investigating the anti-inflammatory and anti-apoptotic role of exosomal miRNA delivery in SAH models, specifically targeting the common pathway identified by the authors.
Topics: Anti-Inflammatory Agents; Brain Injuries; Brain-Derived Neurotrophic Factor; Exosomes; Humans; MicroRNAs; NF-kappa B; Subarachnoid Hemorrhage
PubMed: 36084567
DOI: 10.1016/j.jocn.2022.08.025 -
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 -
World Neurosurgery Oct 2021Blood blister aneurysms are small, thin-walled, rapidly growing side-wall aneurysms that have proved particularly difficult to treat, and evidence-based guidance for... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Blood blister aneurysms are small, thin-walled, rapidly growing side-wall aneurysms that have proved particularly difficult to treat, and evidence-based guidance for treatment strategies is lacking. A systematic review and meta-analysis was performed to aggregate the available data and compare the 3 primary treatment modalities.
METHODS
We performed a comprehensive literature search according to PRISMA guidelines followed by an indirect meta-analysis that compares the safety and efficacy of surgical, flow-diverting stents (FDS), and other endovascular approaches for the treatment of ruptured blood blister aneurysms.
RESULTS
A total of 102 studies were included for quantitative synthesis, with sample sizes of 687 treated surgically, 704 treated endovascularly without FDS, and 125 treated via flow diversion. Comparatively, FDS achieved significantly reduced rates of perioperative retreatment compared with both surgical (P = 0.025) and non-FDS endovascular (P < 0.001). The FDS subgroup also achieved a significantly lower incidence of perioperative rebleed (P < 0.001), perioperative hydrocephalus (P = 0.012), postoperative infarction (P = 0.002), postoperative hydrocephalus (P < 0.001), and postoperative vasospasm (P = 0.002) compared with those patients in the open surgical subgroup. Although no significant differences were found among groups on the basis of functional outcomes, angiographic outcomes detailed by rates of radiographic complete occlusion were highest for surgical (90.7%, 262/289) and FDS (89.1%, 98/110) subgroups versus the non-FDS endovascular subgroup (82.7%, 268/324).
CONCLUSIONS
Flow diversion seems to be an effective treatment strategy for ruptured blood blister aneurysms, with lower rates of perioperative complications compared with surgical and other endovascular techniques, but studies investigating long-term outcomes after flow diversion warrant further study.
Topics: Aneurysm, Ruptured; Endovascular Procedures; Humans; Intracranial Aneurysm; Neurosurgical Procedures; Recurrence; Stents; Treatment Outcome
PubMed: 34224880
DOI: 10.1016/j.wneu.2021.06.129 -
Translational Stroke Research Sep 2018In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To... (Review)
Review
In preclinical models, modification of experimental parameters associated with techniques of inducing subarachnoid hemorrhage (SAH) can greatly affect outcomes. To analyze how parameter choice affects the relevance and comparability of findings, we systematically reviewed 765 experimental studies of in vivo animal SAH models (2000-2014). During the last decade, we found marked increases in publications using smaller species and models for simulating acute events after SAH. Overall, the fewer types of species and models used did not correlate with an increased standardization in the experimental characteristics and procedures. However, by species, commonly applied, reliable parameters for each experimental SAH technique were identified in mouse, rat, rabbit, and dog models. Our findings can serve as a starting point for discussion toward a more uniform performance of SAH experiments, development of preclinical SAH common data elements, and establishment of standardized protocols for multicenter preclinical trials.
PubMed: 30209798
DOI: 10.1007/s12975-018-0657-4 -
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 -
World Neurosurgery Jan 2016Hyponatremia is a common metabolic disturbance after aneurysmal subarachnoid hemorrhage (SAH), and it may worsen outcomes. This review aims to characterize the effect of... (Review)
Review
BACKGROUND
Hyponatremia is a common metabolic disturbance after aneurysmal subarachnoid hemorrhage (SAH), and it may worsen outcomes. This review aims to characterize the effect of hyponatremia on morbidity and mortality after SAH.
OBJECTIVES
We sought to determine the prevalence of hyponatremia after SAH, including in subgroups, as well as its effect on mortality and certain outcome measures, including degree of disability and duration of hospitalization.
METHODS
A search of terms "hyponatremia" and "subarachnoid hemorrhage" was performed on PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and EMBASE. Studies were included if they reported prevalence of hyponatremia and if they discussed outcomes such as mortality, duration of stay, functional outcomes (e.g., Glasgow Outcomes Scale), or incidence of complications in patients with aneurysmal SAH. Two independent researchers assessed the titles and abstracts and reviewed articles for inclusion.
RESULTS
Thirteen studies met inclusion criteria. The prevalence of at least mild hyponatremia was 859 of 2387 (36%) of patients. Hyponatremia was associated with vasospasm and duration of hospitalization, but it did not influence mortality.
CONCLUSION
Hyponatremia is common after SAH, and there is evidence that it is associated with certain poorer outcomes. Larger, prospective studies are needed to assess these findings and provide further evidence.
Topics: Cause of Death; Disability Evaluation; Humans; Hyponatremia; Intracranial Aneurysm; Length of Stay; Subarachnoid Hemorrhage; Survival Analysis
PubMed: 26361321
DOI: 10.1016/j.wneu.2015.08.054 -
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 -
Journal of the Neurological Sciences Jan 2014Previous studies with small sample size have shown that cilostazol can reduce the risk of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH).... (Meta-Analysis)
Meta-Analysis Review
Previous studies with small sample size have shown that cilostazol can reduce the risk of cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage (SAH). The purpose of this study was to determine whether cilostazol is effective in patients with aneurysmal SAH. Studies investigating the effect of cilostazol in patients with aneurysmal SAH were identified using Embase.com without language or publication-type restrictions. We used the random-effect model to combine data. Pooled risk ratios (RR) and 95% confidence intervals (CI) were calculated. Two randomized controlled trials and two quasi-randomized controlled trials with a total of 340 patients were included. The incidence of symptomatic vasospasm (RR=0.47; 95% CI, 0.31-0.72; p<0.001), severe vasospasm (RR=0.48; 95% CI, 0.28-0.82; p=0.007), vasospasm-related new cerebral infarctions (RR=0.38; 95% CI, 0.22-0.67; p=0.001), and poor outcome (RR=0.57; 95% CI, 0.37-0.88; p=0.011) were significantly lower in the cilostazol group. The numbers needed to treat for these outcomes were 6.4, 6.3, 5.7, and 5.4, respectively. Mortality rate differences between the two groups were insignificant. No statistical heterogeneity was found for all outcomes. These results show that cilostazol can decrease the incidence of symptomatic vasospasm, severe vasospasm, vasospasm-related new cerebral infarctions, and poor outcome in patients with aneurysmal SAH.
Topics: Cilostazol; Humans; Intracranial Aneurysm; Neuroprotective Agents; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Tetrazoles; Treatment Outcome
PubMed: 24211059
DOI: 10.1016/j.jns.2013.10.027 -
Translational Stroke Research Dec 2020As a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists... (Meta-Analysis)
Meta-Analysis
As a result of increased awareness of wide-spread methodological bias and obvious translational roadblocks in subarachnoid hemorrhage (SAH) research, various checklists and guidelines were developed over the past decades. This systematic review assesses the overall methodological quality of preclinical SAH research. An electronic search for preclinical studies on SAH revealed 3415 potential articles. Of these, 765 original research papers conducted in vivo in mice, rats, rabbits, cats, dogs, pigs, goats, and non-human primates with a focus on brain damage related to delayed cerebral vasospasm and early brain injury met the inclusion criteria. We found methodological shortcomings still to prevail in preclinical SAH research. In addition, basic animal characteristics were typically well described but important technical parameters of SAH induction were often underreported. None of the species, models, or techniques used in preclinical SAH research was methodologically superior to the others. Methodological quality of preclinical SAH research was independent of the number of citations or impact factor of a publication. Consequently, we suggest the SAH research community should consider strategies to improve preclinical research quality in their field, such as public platforms to (pre)register preclinical experiments, consequent support of open science policies, stricter editorial (and reviewer) control of (pre)existing guidelines, and increased efforts in education and training of good laboratory practice for the next generation of researchers.
Topics: Animals; Disease Models, Animal; Subarachnoid Hemorrhage
PubMed: 32172515
DOI: 10.1007/s12975-020-00801-4