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Neurocritical Care Jun 2022Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with... (Meta-Analysis)
Meta-Analysis Review
Our objective was to compare the effectiveness of intravenous and enteral nimodipine in preventing poor outcome from delayed cerebral ischemia in patients with subarachnoid hemorrhage. We performed a systematic search and a network meta-analysis using the following databases: PubMed, Scopus, the Cochrane Central Register of Controlled Trials, and Google Scholar. Risk of Bias 2 tool was used to assess risk of bias of included studies. A ranking among methods was performed on the basis of the frequentist analog of the surface under the cumulative ranking curve. Published studies that met the following population, intervention, comparison, outcomes and study (PICOS) criteria were included: patients with subarachnoid hemorrhage aged 15 years or older (P); nimodipine, intravenous and oral formulation (I); placebo or no intervention (C); poor outcome measured at 3 months (defined as death, vegetative state, or severe disability), case fatality at 3 months, delayed cerebral ischemia, delayed ischaemic neurologic deficit, and vasospasm measured with transcranial Doppler or digital subtraction angiography (O); and randomized controlled trials (S). No language or publication date restrictions were applied. Ten studies were finally included, with a total of 1527 randomly assigned patients. Oral and intravenous nimodipine were both effective in preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. Neither treatment was effective in improving case fatality. Evolving clinical protocols over a 30-year period and the risk of bias of the included studies may limit the strength of our results. Enteral and intravenous nimodipine may have a similar effectiveness in terms of preventing poor outcome, delayed cerebral ischemia, and delayed ischaemic neurological deficit. More research may be needed to fully establish the role of intravenous nimodipine in current clinical practice.
Topics: Brain Ischemia; Cerebral Infarction; Humans; Network Meta-Analysis; Nimodipine; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial
PubMed: 35419702
DOI: 10.1007/s12028-022-01493-4 -
Journal of the American Heart... Apr 2022Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary... (Meta-Analysis)
Meta-Analysis Review
Background A relevant proportion of patients with suspected coronary artery disease undergo invasive coronary angiography showing normal or nonobstructive coronary arteries. However, the prevalence of coronary microvascular disease (CMD) and coronary spasm in patients with nonobstructive coronary artery disease remains to be determined. The objective of this study was to determine the prevalence of coronary CMD and coronary vasospastic angina in patients with no obstructive coronary artery disease. Methods and Results A systematic review and meta-analysis of studies assessing the prevalence of CMD and vasospastic angina in patients with no obstructive coronary artery disease was performed. Random-effects models were used to determine the prevalence of these 2 disease entities. Fifty-six studies comprising 14 427 patients were included. The pooled prevalence of CMD was 0.41 (95% CI, 0.36-0.47), epicardial vasospasm 0.40 (95% CI, 0.34-0.46) and microvascular spasm 24% (95% CI, 0.21-0.28). The prevalence of combined CMD and vasospastic angina was 0.23 (95% CI, 0.17-0.31). Female patients had a higher risk of presenting with CMD compared with male patients (risk ratio, 1.45 [95% CI, 1.11-1.90]). CMD prevalence was similar when assessed using noninvasive or invasive diagnostic methods. Conclusions In patients with no obstructive coronary artery disease, approximately half of the cases were reported to have CMD and/or coronary spasm. CMD was more prevalent among female patients. Greater awareness among physicians of ischemia with no obstructive coronary arteries is urgently needed for accurate diagnosis and patient-tailored management.
Topics: Coronary Angiography; Coronary Artery Disease; Coronary Vasospasm; Coronary Vessels; Female; Humans; Male; Microcirculation; Microvascular Angina; Prevalence
PubMed: 35301851
DOI: 10.1161/JAHA.121.023207 -
Neurocritical Care Oct 2019Intrathecal nicardipine has been shown to have some efficacy for the treatment of symptomatic cerebral vasospasm in aneurysmal subarachnoid hemorrhage (aSAH). We...
Intrathecal nicardipine has been shown to have some efficacy for the treatment of symptomatic cerebral vasospasm in aneurysmal subarachnoid hemorrhage (aSAH). We performed a PRISMA-based systematic review of intrathecal nicardipine for the treatment of cerebral vasospasm in aneurysmal subarachnoid hemorrhage. A total of 825 articles were reviewed. After duplicates were removed and the search criteria was applied, 9 articles remained that were eligible for inclusion and analysis. 377 patients received a total of 6,596 injections of intrathecal nicardipine for aSAH-related cerebral vasospasm. The cumulative ventriculostomy-associated infection risk was 6%. Intrathecal nicardipine injections for aSAH-related cerebral vasospasm appears efficacious and safe. Administration of 4 mg of nicardipine every 12 hours was the most commonly reported dosing regimen. Intrathecal nicardipine decreases mean flow velocities on transcranial Doppler and reduces angiographic and clinical vasospasm. The infection risk appears to be in-line with studies in which rates of EVD-related infections have been reported.
Topics: Blood Flow Velocity; Cerebrovascular Circulation; Humans; Injections, Intraventricular; Injections, Spinal; Nicardipine; Subarachnoid Hemorrhage; Treatment Outcome; Ultrasonography, Doppler, Transcranial; Vasodilator Agents; Vasospasm, Intracranial; Ventriculostomy
PubMed: 30607826
DOI: 10.1007/s12028-018-0659-9 -
Stroke Jun 2022Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Aneurysmal subarachnoid hemorrhage (aSAH) is associated with high mortality and morbidity. We aimed to determine the relative benefits of pharmacological prophylactic treatments in patients with aneurysmal subarachnoid hemorrhage by performing a network meta-analysis of randomized trials.
METHODS
We searched Medline, Web of Science, Embase, Scopus, ProQuest, and Cochrane Central to February 2020. Pairs of reviewers independently identified eligible trials, extracted data, and assessed the risk of bias. Eligible trials compared the prophylactic effects of any oral or intravenous medications or intracranial drug-eluting implants to one another or placebo or standard of care in adult hospitalized patients with confirmed aneurysmal subarachnoid hemorrhage. We used the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach to assess the certainty of the evidence.
RESULTS
We included 53 trials enrolling 10 415 patients. Nimodipine likely reduces all-cause mortality compared to placebo (odds ratio [OR],0.73 [95% CI, 0.53-1.00]; moderate certainty; absolute risk reduction (ARR), -3.35%). Nimodipine (OR, 1.46 [95% CI, 1.07-1.99]; high certainty; absolute risk increase, 8.25%) and cilostazol (OR, 3.73 [95% CI, 1.14-12.18]; moderate certainty; absolute risk increase, 23.15%) were the most effective treatments in improving disability at the longest follow-up. Compared to placebo, clazosentan (10 mg/kg; OR, 0.39 [95% CI, 0.22-0.68]; high certainty; ARR, -16.65%), nicardipine (OR, 0.48 [95% CI, 0.24-0.94]; moderate certainty; ARR, -13.70%), fasudil (OR, 0.55 [95% CI, 0.31-0.98]; moderate certainty; ARR, -11.54%), and magnesium (OR, 0.66 [95% CI, 0.46-0.94]; high certainty; ARR, -8.37%) proved most effective in reducing the likelihood of delayed cerebral ischemia.
CONCLUSIONS
Nimodipine and cilostazol are likely the most effective treatments in preventing morbidity and mortality in patients with aneurysmal subarachnoid hemorrhage. Clazosentan, nicardipine, fasudil, and magnesium showed beneficial effects on delayed cerebral ischemia and vasospasm but they were not found to reduce mortality or disability. Future trials are warranted to elaborately investigate the prophylactic effects of medications that may improve mortality and long-term functional outcomes, such as cilostazol and clazosentan.
REGISTRATION
URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019122183.
Topics: Adult; Brain Ischemia; Cilostazol; Humans; Magnesium; Morbidity; Network Meta-Analysis; Nicardipine; Nimodipine; Randomized Controlled Trials as Topic; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 35354302
DOI: 10.1161/STROKEAHA.121.035699 -
Neurosurgery Dec 2023Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND OBJECTIVES
Clazosentan has been studied to treat cerebral vasospasm after aneurysmal subarachnoid hemorrhage (aSAH).This meta-analysis of randomized controlled trials updates the current knowledge regarding the efficacy and safety of clazosentan compared with placebo after aSAH.
METHODS
Databases were systematically searched for randomized controlled trials directly comparing the use of clazosentan and placebo for the treatment of cerebral vasospasm after aSAH. Additional eligibility criteria were the report of any of the outcomes of interest (vasospasm, morbidity, functional outcome, or mortality). The primary outcome was vasospasm-related delayed cerebral ischemia (DCI). The analyses were stratified by clazosentan dosage (low or high dose) and aneurysm treatment modality (clipping or coiling). The Cochrane RoB-2 tool was used for studies quality assessment.
RESULTS
Six studies comprising 7 clinical trials were included, involving 2778 patients. Clazosentan decreased the risk of vasospasm-related DCI (risk ratio [RR] 0.56, 95% CI 0.38-0.81) and delayed ischemic neurological deficit (RR 0.63, 95% 0.50-0.80). Angiographic vasospasm (RR 0.54, 95% CI 0.47-0.61) was also decreased. Functional outcomes (favorable Glasgow Outcome Scale, RR 0.99, 95% CI 0.79-1.24) and death (RR 1.03, 95% CI 0.71-1.49) did not change. Meanwhile, adverse events were increased by clazosentan (RR 1.54, 95% CI 1.35-1.76).
CONCLUSION
Clazosentan decreased vasospasm-related DCI and angiographic vasospasm but did not improve functional outcomes or mortality. Adverse events were increased by clazosentan.
Topics: Humans; Subarachnoid Hemorrhage; Treatment Outcome; Vasospasm, Intracranial; Dioxanes; Brain Ischemia; Cerebral Infarction
PubMed: 37462365
DOI: 10.1227/neu.0000000000002601 -
Frontiers in Neurology 2023Vasospasm and cerebral ischemia after aneurysmal subarachnoid hemorrhage are associated with mortality and poor neurological outcomes. We studied the efficacy of all...
BACKGROUND
Vasospasm and cerebral ischemia after aneurysmal subarachnoid hemorrhage are associated with mortality and poor neurological outcomes. We studied the efficacy of all available strategies targeting vasospasm and cerebral ischemia on outcomes in a network meta-analysis.
METHODS
We searched EMBASE and MEDLINE databases from 1 January 1990 and 28 November 2021 according to PRISMA guidelines. Randomized controlled trials and longitudinal studies were included. All curative or preventive strategies targeting vasospasm and/or cerebral ischemia were eligible. A network meta-analysis was performed to compare all interventions with one another in a primary (randomized controlled trials only) and a secondary analysis (both trials and longitudinal studies). Mortality by 3 months was the primary outcome. Secondary outcomes were vasospasm, neurological outcome by 3 months, and dichotomized as "good" or "poor" recovery according to each study definition.
RESULTS
A total of 2,382 studies were screened which resulted in the selection of 192 clinical trials (92 (47.9%) and 100 cohorts (52.1%) and the inclusion of 41,299 patients. In randomized controlled studies, no strategy decreased mortality by 3 months. Statins (0.79 [0.62-1]), tirilazad (0.82 [0.69-0.97]), CSF drainage (0.47 [0.29-0.77]), and clazosentan (0.51 [0.36-0.71]) significantly decreased the incidence of vasospasm. Cilostazol was the only treatment associated with improved neurological outcomes by 3 months in the primary (OR 1.16, 95% CI [1.05-1.28]) and secondary analyses (OR 2.97, 95% CI [1.39-6.32]).
DISCUSSION
In the modern era of subarachnoid hemorrhage, all strategies targeting vasospasm failed to decrease mortality. Cilostazol should be confirmed as a treatment to improve neurological outcomes. The link between vasospasm and neurological outcome appears questionable.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=116073, identifier: PROSPERO CRD42018116073.
PubMed: 37662039
DOI: 10.3389/fneur.2023.1217719 -
Regional Anesthesia and Pain Medicine Oct 2023Delayed cerebral ischemia (DCI) is the second-leading cause of death and disability in patients with aneurysmal subarachnoid hemorrhage (aSAH), and is associated with... (Review)
Review
BACKGROUND/IMPORTANCE
Delayed cerebral ischemia (DCI) is the second-leading cause of death and disability in patients with aneurysmal subarachnoid hemorrhage (aSAH), and is associated with cerebral arterial vasospasm (CAV). Current treatments for CAV are expensive, invasive, and have limited efficacy. Cervical sympathetic block (CSB) is an underappreciated, but potentially highly effective therapy for CAV.
OBJECTIVE
To provide a comprehensive review of the preclinical and human literature pertinent to CSB in the context of CAV.
EVIDENCE REVIEW
This study followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guidelines. We conducted a literature search using Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Scopus and Web of Science until February 2022, to identify abstracts, conference proceedings, and full-text papers pertinent to cervical sympathectomy and CAV in animal/adult patients.
FINDINGS
We included six human and six experimental studies. Human studies were mostly prospective observational, except one retrospective and one randomized clinical trial, and used various imaging modalities to measure changes in arterial diameter after the block. Studies that used digital subtraction angiography showed an improvement in cerebral perfusion without change in vessel diameter. Transcranial Doppler studies found an approximately 15% statistically significant decrease in velocities consistent with arterial vasodilatation. Overall, the results suggest an increase in cerebral arterial diameter and neurological improvement in patients receiving a CSB. Animal studies demonstrate that sympathetic system ablation vasodilates cerebral vasculature and decreases the incidence of symptomatic vasospasm.
CONCLUSIONS
This scoping review suggests that CSB may be a viable option for treatment and prevention of CAV/DCI in patients with aSAH, although the included studies were heterogeneous, mostly observational, and with a small sample size. Further research is needed to standardize the technique and prove its effectiveness to treat patients suffering of CAV/DCI after aSAH.
Topics: Adult; Humans; Retrospective Studies; Vasospasm, Intracranial; Subarachnoid Hemorrhage; Brain Ischemia; Sympathectomy; Observational Studies as Topic; Randomized Controlled Trials as Topic
PubMed: 36424089
DOI: 10.1136/rapm-2022-103999 -
Neurosurgical Focus Mar 2022Aneurysmal subarachnoid hemorrhage (aSAH) accounts for a relatively small portion of strokes but has the potential to cause permanent neurological deficits. Vasospasm... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Aneurysmal subarachnoid hemorrhage (aSAH) accounts for a relatively small portion of strokes but has the potential to cause permanent neurological deficits. Vasospasm with delayed ischemic neurological deficit is thought to be responsible for much of the morbidity associated with aSAH. This has illuminated some treatment options that have the potential to target specific components of the vasospasm cascade. Intrathecal management via lumbar drain (LD) or external ventricular drain (EVD) offers unique advantages in this patient population. The aim of this review was to provide an update on intrathecal vasospasm treatments, emphasizing the need for larger-scale trials and updated protocols using data-driven evidence.
METHODS
A search of PubMed, Ovid MEDLINE, and Cochrane databases included the search terms (subarachnoid hemorrhage) AND (vasospasm OR delayed cerebral ischemia) AND (intrathecal OR intraventricular OR lumbar drain OR lumbar catheter) for 2010 to the present. Next, a meta-analysis was performed of select therapeutic regimens. The primary endpoints of analysis were vasospasm, delayed cerebral ischemia (DCI), cerebral infarction, and functional outcome.
RESULTS
Twenty-nine studies were included in the analysis. There were 10 studies in which CSF drainage was the primary experimental group. Calcium channel antagonists were the focus of 7 studies. Fibrinolytics and other vasodilators were each examined in 6 studies. The meta-analysis included studies examining CSF drainage via LD (n = 4), tissue plasminogen activator in addition to EVD (n = 3), intraventricular nimodipine (n = 2), and cisternal magnesium (n = 2). Results showed that intraventricular nimodipine decreased vasospasm (OR 0.59, 95% CI 0.37-0.94; p = 0.03). Therapies that significantly reduced DCI were CSF drainage via LD (OR 0.47, 95% CI 0.25-0.88; p = 0.02) and cisternal magnesium (OR 0.27, 95% CI 0.07-1.02; p = 0.05). CSF drainage via LD was also found to significantly reduce the incidence of cerebral infarction (OR 0.35, 95% 0.24-0.51; p < 0.001). Lastly, functional outcome was significantly better in patients who received CSF drainage via LD (OR 2.42, 95% CI 1.39-4.21; p = 0.002).
CONCLUSIONS
The authors' results showed that intrathecal therapy is a safe and feasible option following aSAH. It has been shown to attenuate cerebral vasospasm, reduce the incidence of DCI, and improve clinical outcome. The authors support the use of intrathecal management in the prevention and rescue management of cerebral vasospasm. More randomized controlled trials are warranted to determine the best combination of pharmaceutical agents and administration route in order to formulate a standardized treatment approach.
Topics: Brain Ischemia; Drainage; Humans; Subarachnoid Hemorrhage; Tissue Plasminogen Activator; Vasospasm, Intracranial
PubMed: 35231885
DOI: 10.3171/2021.12.FOCUS21629 -
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 -
Frontiers in Neuroscience 2023Intracranial aneurysms (IA) are the most common cerebral vascular pathologies. Their rupture leads to the most dangerous subtype of stroke-aneurysmal subarachnoid... (Review)
Review
Intracranial aneurysms (IA) are the most common cerebral vascular pathologies. Their rupture leads to the most dangerous subtype of stroke-aneurysmal subarachnoid hemorrhage (aSAH), which may be followed by cerebral vasospasm and ischemic sequelae. Recently, an imbalance within the intestinal microbiota, referred to as dysbiosis, was suggested to play a role in the formation, progression, and rupture of IA. As no systematic review on this topic exists, considering the significance of this matter and a lack of effective prophylaxis against IA or cerebral vasospasm, we aim to sum up the current knowledge regarding their associations with intestinal microbiome, identify the gaps, and determine future prospects. Scientific databases were systematically and independently searched by two authors from inception to 1st May 2023 for original articles regarding the role of intestinal microbiota in intracranial aneurysmal growth, aSAH occurrence, as well as in cerebral vasospasm following aSAH. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist was followed in an abstraction process. The STROBE tool was applied to assess the risk of bias. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 302 records, four studies were included that fully met eligibility criteria. Studies reported (1) that the relative abundance of is a protective factor against aneurysm growth and rupture, resulting from the reduced inflammation and extracellular matrix remodeling in the cerebral arterial wall and from reduced metalloproteinase-mediated degradation of smooth muscle cells in cerebral vessels. (2) Relative abundance of is associated with aSAH. (3) No article has evaluated microbiota in relation to cerebral vasospasm following aSAH although there is an ongoing study. We concluded that intestinal microbiota might be a potential target for diagnostic and therapeutic tools to improve the management of cerebral aneurysms. However, more studies of prospective design are needed.
PubMed: 37928732
DOI: 10.3389/fnins.2023.1247151