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Fluids and Barriers of the CNS Nov 2023Cerebral vasospasm significantly contributes to poor prognosis and mortality in patients with aneurysmal subarachnoid hemorrhage. Current research indicates that the... (Review)
Review
Cerebral vasospasm significantly contributes to poor prognosis and mortality in patients with aneurysmal subarachnoid hemorrhage. Current research indicates that the pathological and physiological mechanisms of cerebral vasospasm may be attributed to the exposure of blood vessels to toxic substances, such as oxyhaemoglobin and inflammation factors. These factors disrupt cerebral vascular homeostasis. Vascular homeostasis is maintained by the extracellular matrix (ECM) and related cell surface receptors, such as integrins, characterised by collagen deposition, collagen crosslinking, and elastin degradation within the vascular ECM. It involves interactions between the ECM and smooth muscle cells as well as endothelial cells. Its biological activities are particularly crucial in the context of cerebral vasospasm. Therefore, regulating ECM homeostasis may represent a novel therapeutic target for cerebral vasospasm. This review explores the potential pathogenic mechanisms of cerebral vasospasm and the impacts of ECM protein metabolism on the vascular wall during ECM remodelling. Additionally, we underscore the significance of an ECM protein imbalance, which can lead to increased ECM stiffness and activation of the YAP pathway, resulting in vascular remodelling. Lastly, we discuss future research directions.
Topics: Humans; Vasospasm, Intracranial; Endothelial Cells; Extracellular Matrix; Subarachnoid Hemorrhage; Extracellular Matrix Proteins; Collagen
PubMed: 37925414
DOI: 10.1186/s12987-023-00483-8 -
Acta Neurochirurgica. Supplement 2020Key references on the history of vasospasm, a selected bibliography of B.K.A. Weir and colleagues on aneurysms and vasospasm and commentary on the "New World of Thought"...
Key references on the history of vasospasm, a selected bibliography of B.K.A. Weir and colleagues on aneurysms and vasospasm and commentary on the "New World of Thought" are provided.
Topics: Humans; Intracranial Aneurysm; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 31407055
DOI: 10.1007/978-3-030-04615-6_1 -
Neurosurgical Review Aug 2023Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm, significantly associated with morbidity and mortality. In double-blind, placebo-controlled... (Observational Study)
Observational Study
Aneurysmal subarachnoid hemorrhage (aSAH) may lead to cerebral vasospasm, significantly associated with morbidity and mortality. In double-blind, placebo-controlled phase 3 studies, clazosentan reduces cerebral vasospasm-related morbidity and all-cause mortality in patients with aSAH. There are no reports about the clinical efficacy of clazosentan combination therapy with some other drugs. Initially, we explored the efficacy of clazosentan combination therapy with cilostazol, statin, and antiepileptic drugs. Subsequently, we assessed the add-on effect of fasudil to clazosentan combination therapy for aSAH patients. This multicenter, retrospective, observational cohort study included Japanese patients with aSAH between June 2022 and March 2023. The primary outcome was the ordinal score on the modified Rankin Scale (mRS; range, 0-6, with elevated scores indicating greater disability) at discharge. Among the 47 cases (women 74.5%; age 64.4 ± 15.0 years) undergoing clazosentan combination therapy, 29 (61.7%) resulted in favorable outcomes. Overall, vasospasm occurred in 16 cases (34.0%), with four cases (8.5%) developing vasospasm-related delayed cerebral ischemia (DCI). Both hypotension and vasospasm-related DCI were related to unfavorable outcome at discharge. Fasudil were added in 18 (38.3%) cases. Despite adding fasudil to clazosentan combination therapy, the incidence of aSAH-related vasospasm did not decrease. Added-on fasudil to combination therapy related to pulmonary edema, vasospasm, and vasospasm-related DCI, and unfavorable outcomes. Clazosentan combination therapy could potentially result in favorable outcomes for aSAH patients to prevent post-aSAH vasospasm-related DCI. The add-on effect of fasudil to combination therapy did not demonstrate a significant impact in reducing aSAH-related vasospasm or improving outcomes at discharge.
Topics: Aged; Female; Humans; Middle Aged; Brain Ischemia; Cerebral Infarction; Retrospective Studies; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 37555872
DOI: 10.1007/s10143-023-02104-2 -
CNS Neuroscience & Therapeutics Oct 2019Aneurysmal subarachnoid hemorrhage (aSAH) continues to be associated with significant morbidity and mortality despite advances in care and aneurysm treatment strategies.... (Review)
Review
Aneurysmal subarachnoid hemorrhage (aSAH) continues to be associated with significant morbidity and mortality despite advances in care and aneurysm treatment strategies. Cerebral vasospasm continues to be a major source of clinical worsening in patients. We intended to review the clinical and experimental aspects of aSAH and identify strategies that are being evaluated for the treatment of vasospasm. A literature review on aSAH and cerebral vasospasm was performed. Available treatments for aSAH continue to expand as research continues to identify new therapeutic targets. Oral nimodipine is the primary medication used in practice given its neuroprotective properties. Transluminal balloon angioplasty is widely utilized in patients with symptomatic vasospasm and ischemia. Prophylactic "triple-H" therapy, clazosentan, and intraarterial papaverine have fallen out of practice. Trials have not shown strong evidence supporting magnesium or statins. Other calcium channel blockers, milrinone, tirilazad, fasudil, cilostazol, albumin, eicosapentaenoic acid, erythropoietin, corticosteroids, minocycline, deferoxamine, intrathecal thrombolytics, need to be further investigated. Many of the current experimental drugs may have significant roles in the treatment algorithm, and further clinical trials are needed. There is growing evidence supporting that early brain injury in aSAH may lead to significant morbidity and mortality, and this needs to be explored further.
Topics: Calcium Channel Blockers; Endovascular Procedures; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Subarachnoid Hemorrhage; Vasodilator Agents; Vasospasm, Intracranial
PubMed: 31583833
DOI: 10.1111/cns.13222 -
Current Neurovascular Research 2021The correlation of neuroinflammation with the development of cerebral vasospasm following subarachnoid hemorrhage has been well documented in the literature; both... (Review)
Review
The correlation of neuroinflammation with the development of cerebral vasospasm following subarachnoid hemorrhage has been well documented in the literature; both clinical and preclinical. The exact mechanisms by which this process occurs, however, are poorly elucidated. Recent evidence indicates that interleukin-6 is not only an important prognostic biomarker for subarachnoid hemorrhage and subsequent vasospasm development but also an integral component in the progression of injury following initial insult. In this review, we briefly highlight other pathways under investigation and focus heavily on what has been discovered regarding the role of interleukin 6 and cerebral vasospasm following subarachnoid hemorrhage. A proposed mechanistic pathway is highlighted in written and graphical format. A discussion regarding the human correlative findings and initial pre-clinical mechanistic studies is addressed. Finally, in the future investigation section, innovative developments and a clear description of areas warranting further scientific inquiry are emphasized. This review will catalyze continued discovery in this area of emerging significance and aid in the quest for effective vasospasm treatment where limited clinical therapeutics currently exist.
Topics: Humans; Interleukin-6; Subarachnoid Hemorrhage; Vasospasm, Intracranial
PubMed: 34736380
DOI: 10.2174/1567202618666211104122408 -
Frontiers in Neuroscience 2022Cerebral vasospasm is a frequently encountered clinical problem, especially in patients with traumatic brain injury and subarachnoid hemorrhage. Continued cerebral... (Review)
Review
Cerebral vasospasm is a frequently encountered clinical problem, especially in patients with traumatic brain injury and subarachnoid hemorrhage. Continued cerebral vasospasm can cause cerebral ischemia, even infarction and delayed ischemic neurologic deficits. It significantly affects the course of the disease and the outcome of the patient. However, the underlying mechanism of cerebral vasospasm is still unclear. Recently, increasing studies focus on the pathogenic mechanism of microparticles. It has been found that microparticles have a non-negligible role in promoting vasospasm. This research aims to summarize the dynamics of microparticles and identify a causal role of microparticles in the occurrence and development of cerebral vasospasm. We found that these various microparticles showed dynamic characteristics in body fluids and directly or indirectly affect the cerebral vasospasm or prompt it. Due to the different materials carried by microparticles from different cells, there are also differences in the mechanisms that lead to abnormal vasomotor. We suggest that microparticle scavengers might be a promising therapeutic target against microparticles associated complications.
PubMed: 36389239
DOI: 10.3389/fnins.2022.1013437 -
Clinical Physiology and Functional... Jan 2023Subarachnoid haemorrhage (SAH) is a cerebrovascular emergency associated with significant morbidity and mortality. SAH is characterized by heterogeneity, interindividual... (Review)
Review
Subarachnoid haemorrhage (SAH) is a cerebrovascular emergency associated with significant morbidity and mortality. SAH is characterized by heterogeneity, interindividual variation and complexity of pathophysiological responses following extravasation of blood from cerebral circulation. The purpose of this review is to integrate previously established pre-existing factors, pathophysiological pathways and to develop a concept map of mechanisms of SAH-induced cerebral vasospasm and delayed cerebral ischaemia using a systematic approach. We conducted an extensive mapping of a hypothesized sequence of pathophysiological events. Documentation of supporting evidence was done alongside a concept map building. After finalizing the model, we conducted an analysis of the consequences and connections of pathophysiological events. We included the findings of experimental research, focusing on pathophysiological processes. We focused on SAH-induced cerebral vasospasm and delayed cerebral ischaemia as a component of cerebral injury and potential systemic consequences. SAH-induced brain injury occurs within 72 h following haemorrhage. Pathophysiology of cerebral vasospasm may include reduction in NO production, direct activation of calcium channels, upregulating genes involved with inflammation and extracellular matrix remodelling, triggering oxidative stress and free radical damage to smooth muscle and lipid peroxidation of cell membranes, cortical spreading depolarizations, sympathetic activation, finally resulting in the failure of cerebral autoregulation, microthrombosis and cerebral ischaemic injury. This cascade of events might explain why medical therapy often fails to reverse resistant cerebral vasospasm and to prevent cerebral ischaemia.
Topics: Humans; Vasospasm, Intracranial; Subarachnoid Hemorrhage; Brain Ischemia
PubMed: 36082805
DOI: 10.1111/cpf.12787 -
Neurocritical Care Aug 2022Following aneurysmal subarachnoid hemorrhage (SAH), patients are monitored closely for vasospasm in the intensive care unit. Conditional vasospasm-free survival...
BACKGROUND
Following aneurysmal subarachnoid hemorrhage (SAH), patients are monitored closely for vasospasm in the intensive care unit. Conditional vasospasm-free survival describes the risk of future vasospasm as a function of time elapsed without vasospasm. Conditional survival has not been applied to this clinical scenario but could improve patient counseling and intensive care unit use. The objective of this study was to characterize conditional vasospasm-free survival following SAH.
METHODS
This was a single institution, retrospective cohort study of patients treated for aneurysmal SAH between 1/1/2000-6/1/2020. The primary outcome was the development of vasospasm defined by the first instance of either radiographic vasospasm on computed tomography angiography, Lindegaard Index > 3.0 by transcranial doppler ultrasonography, or vasospasm-specific intraarterial therapy. Multivariable Cox regression was performed, and conditional vasospasm-free survival curves were constructed.
RESULTS
A total of 528 patients were treated for aneurysmal SAH and 309 (58.5%) developed vasospasm. Conditional survival curves suggest patients who survive to postbleed day 10 without vasospasm have a nearly 90% chance of being discharged without vasospasm. The median onset of vasospasm was postbleed day 6. Age more than 50 years was associated with a lower risk (hazard ratio [HR] = .76; 95% confidence interval [CI] 0.64-0.91; p < 0.001). Higher initial systolic blood pressure (HR = 1.18; 95% CI 1.046-1.350; p = .008), Hunt-Hess grades 4 or 5 (HR = 1.304; 95% CI 1.014-1.676), and modified Fisher scale score of 4 (HR = 1.808; 95% CI 1.198-2.728) were associated with higher vasospasm than the respective lower grades.
CONCLUSION
Conditional survival provides a useful framework for counseling patients and making decisions around vasospasm risk for patients with aneurysmal SAH, while risk factor-stratified plots facilitate a patient-centric, evidence-based approach to these conversations and decisions.
Topics: Autonomic Nervous System Diseases; Humans; Middle Aged; Retrospective Studies; Risk Factors; Subarachnoid Hemorrhage; Ultrasonography, Doppler, Transcranial; Vasospasm, Intracranial
PubMed: 35099712
DOI: 10.1007/s12028-022-01444-z -
Neuromodulation : Journal of the... Dec 2022Cerebral vasospasm is a severe and potentially lethal complication in patients with subarachnoid hemorrhage (SAH). Its pathogenesis is still not completely understood.... (Review)
Review
OBJECTIVES
Cerebral vasospasm is a severe and potentially lethal complication in patients with subarachnoid hemorrhage (SAH). Its pathogenesis is still not completely understood. The efficacy of current treatments, such as triple-H therapy or calcium channel blockers, is unsatisfactory, and a new therapy model would therefore be valuable. Electrical stimulation may have a considerable influence on cerebrovascular innervation. This systematic review gives an overview of the studies that have applied electrical stimulation in models of cerebral vasospasm.
MATERIALS AND METHODS
We performed a systematic review of the literature, searching PubMed and Ovid Embase with the keywords "electric stimulation," "cerebral vasospasm," "subarachnoid hemorrhage," "sympathetic," and "parasympathetic." Additional papers were identified from the reference lists of the articles identified in the literature search.
RESULTS
Increased cerebral blood flow (CBF) is a widely observed effect of spinal cord stimulation and sphenopalatine ganglion stimulation in models of physiological conditions or experimental cerebral vasospasm. Most studies were conducted in animals, 15 under physiological conditions and 11 in animals with SAH. Eight studies in humans were identified that examined the stimulation effect on CBF under physiological conditions. Only two studies looked at patients after SAH: one applied spinal cord stimulation (SCS) and the other transcutaneous electrical neurostimulation. Different mechanisms leading to stimulation-induced CBF increase that were discussed included "reversible functional sympathectomy," activation of brainstem vasomotor centers, involvement of central ascending pathways, release of neurohumoral factors, and interaction with sympathetic, parasympathetic, and trigeminal innervation. The results indicate that electrical stimulation is a promising procedure for prevention and treatment of cerebral vasospasm.
CONCLUSION
Electrical stimulation, especially SCS and sphenopalatine ganglion stimulation, is a promising adjunct for existing therapies for vasospasm after SAH. Further experiments and prospective clinical studies are needed to establish its potential usefulness as a therapy or prevention option.
Topics: Humans; Animals; Vasospasm, Intracranial; Subarachnoid Hemorrhage; Prospective Studies; Electric Stimulation; Ganglia, Parasympathetic
PubMed: 35382977
DOI: 10.1016/j.neurom.2022.01.020 -
Critical Care Science 2023To determine the prevalence of sonographic vasospasm and delayed ischemic deficit in patients with aneurysmal subarachnoid hemorrhage, to evaluate the correlation...
OBJECTIVE
To determine the prevalence of sonographic vasospasm and delayed ischemic deficit in patients with aneurysmal subarachnoid hemorrhage, to evaluate the correlation between different tomographic scales and these complications, and to study prognostic factors in this group of patients.
METHODS
This was a prospective study of patients admitted to the intensive care unit with a diagnosis of aneurysmal subarachnoid hemorrhage. The prevalence of sonographic vasospasm and radiological delayed cerebral ischemia was analyzed, as was the correlation between different tomographic scales and these complications.
RESULTS
A total of 57 patients were studied. Sixty percent of the patients developed sonographic vasospasm, which was significantly associated with delayed cerebral ischemia and mortality. The Claassen and Hijdra scales were better correlated with the development of cerebral vasospasm (areas under the curve of 0.78 and 0.68) than was Fisher's scale (0.62). Thirty-two patients (56.1%) developed cerebral infarction on CT; the significantly associated factors were poor clinical grade at admission (p = 0.04), sonographic vasospasm (p = 0.008) and severity of vasospasm (p = 0.015). Only the semiquantitative Hijdra scale was significantly correlated with the development of radiological delayed cerebral ischemia (p = 0.009). The patients who presented cerebral infarction had worse neurological evolution and higher mortality.
CONCLUSION
This is the first study in our environment on the subject. The Claassen and Hijdra tomographic scales showed better prognostic performance than the Fisher scale for the development of cerebral vasospasm. The finding of sonographic vasospasm could be a noninvasive criterion for the early detection of delayed cerebral ischemia and neurological deterioration in patients with aneurysmal subarachnoid hemorrhage.
Topics: Humans; Subarachnoid Hemorrhage; Vasospasm, Intracranial; Prospective Studies; Brain Ischemia; Cerebral Infarction
PubMed: 38133161
DOI: 10.5935/2965-2774.20230119-en