Original ArticleRisk Factors for Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage: A Review of the Literature
Introduction
The incidence of aneurysmal subarachnoid hemorrhage (SAH) is higher in Japan than in Western countries; SAH incidence increases with age and is more common among women than men.1, 2 In Izumo City, Japan, during the years 1980–1998, the crude and age-adjusted and sex-adjusted incidence rates of aneurysmal SAH were both 23 per 100,000 people per year for all ages.2 During the years 1987–1992, when including in the incidence calculations patients whose death certificates indicated that they might have died of aneurysmal SAH, but who had not been formally examined, the rates increased to 32 and 29 per 100,000 people per year, respectively.1 During the 9-year period 1990–1998, although the 6-month case-fatality rate in surgically treated patients was only 2%, the overall case-fatality rate was 38%, and the functional outcome was still unsatisfactory.3 In other words, despite advances in diagnostic, neurosurgical, and anesthetic techniques as well as preoperative and postoperative management of patients, the ultimate overall outcome in patients with aneurysmal SAH remains unsatisfactory.
Cerebral vasospasm (CV) is a leading cause of morbidity and mortality after SAH, even after a ruptured aneurysm has been secured by microsurgical clipping or endovascular coiling. Current surgical and medical treatments fail to prevent or reverse CV consistently largely because the pathogenesis of this condition is multifocal and complex and is not yet fully understood. It is important to identify risk factors and markers for CV and to develop better means of predicting it, allowing more effective treatment. CV after SAH has been defined by various terms, including angiographic vasospasm (AV), symptomatic vasospasm (SV), cerebral infarction (CI) on computed tomography (CT) scan, delayed cerebral ischemia (DCI), and delayed ischemic neurologic deficit (DIND), among other terms. However, no previous review studies investigated the individual relationships between risk factors and AV, SV, CI, DCI, and DIND. Taking into consideration these points, the aim of the present study was to review the risk factors and markers for CV after SAH.
Section snippets
Materials and Methods
A comprehensive literature survey of the risk factors associated with the occurrence of CV after aneurysmal SAH was performed using standard search engines, including PubMed. The present study addresses the definition of CV and discusses the relationships between risk factors and each individually defined type of CV. Included are 7 animal experimental studies relating to the effects of aging,4 rebleeding,5 level of interleukin-6 (IL-6) in cerebrospinal fluid (CSF) and serum,6, 7, 8, 9 and
Definition of CV
AV is usually based on subjective narrowing of the artery compared with images without vasospasm,26, 31, 34, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64 as first described by Ecker and Riemenschneider in 1951.65 Harrod et al.66 stated that conventional angiography is the gold standard for definitive diagnosis of CV. Vergouwen et al.64 maintained that the term vasospasm should be reserved for angiographic arterial narrowing. In most recent studies, patients
Age
Although some studies suggested that the incidence of AV is slightly lower in elderly patients,51, 57, 60, 71, 100 most authors maintained that there is no correlation between the incidence or severity of vascular narrowing and patient age.26, 31, 34, 52, 68, 101, 102 Advanced age is reportedly associated with a lower incidence of SV,14, 16, 20, 33, 57, 60, 98, 103 DCI,30 DIND,103, 104 or CV defined by clinical and radiologic criteria27 compared with observations in younger patients, although
Clinical Grade
With regard to clinical grade, positive associations were reported between Hunt and Hess grade and AV,47, 71 SV,14, 22, 23, 41, 71 DCI,71 or CV defined by clinical and radiologic criteria27 and between World Federation of Neurosurgical Societies grade and SV,20, 24, 52 CI,25 or DCI.30 In contrast, 2 studies showed that clinically low Hunt and Hess14 or World Federation of Neurosurgical Societies16 grade was a predictor of SV. However, most studies showed no consistent relationships between Hunt
Heart Disease
One study demonstrated a significant relationship between a history of cardiovascular disease and DCI,13 whereas most studies found no relationship between heart disease and AV,31 SV,15, 23, 31, 33 CI,25, 31 or DCI.17, 19, 28
Diabetes Mellitus
In 2 studies, a significant association was found between diabetes mellitus and SV69 or CI,25 whereas other studies found no effect of diabetes mellitus on AV,26 SV,15, 21, 22, 23, 29, 31, 33, 106 DCI,19, 28, 30 or DIND.37 Dumont et al.69 reported that preexisting diabetes
Severity of SAH Clot on CT Scan
In 1968, when CT scan was unavailable, Wilkins et al.102 reported that intracranial arterial spasm was seen most frequently in conjunction with SAH and that it seemed to be roughly related to the amount of blood in the subarachnoid spaces enclosing the circle of Willis. At the present time, there is undoubtedly a strict correlation between the amount of subarachnoid blood detected by CT scan soon after SAH and the subsequent development of CV, regardless of the definition of CV.11, 12, 13, 14,
Leukocytosis
Some authors stated that leukocytosis is a risk factor for the development of SV,21, 128, 129 DCI,79 DIND,130 or delayed neurologic deterioration91 after SAH, whereas others indicated that it is not a risk factor for AV,31 SV,18, 29, 31, 106 CI,31 DIND,87 or ischemic complications.89 Weir et al.91 reported that more severe leukocytosis was correlated with an increased incidence of delayed neurologic deterioration and mortality. Rothoerl et al.130 showed that white blood cell counts and
Electrocardiogram Changes
Electrocardiogram (ECG) abnormalities after SAH have been well documented. ECG changes including Q–Tc prolongation, ST-T segment changes, and U wave abnormalities occur during the acute phase of SAH and appear to be related to transient cardiac dysfunction.139, 140, 141, 142 It has been suggested that stimulation of the hypothalamus by SAH elevates the serum levels of catecholamines and excites the sympathetic nerves, leading to repolarization abnormalities, impaired systolic and diastolic
Clipping Versus Coiling
In patients who undergo early aneurysm clipping, surgical clot removal, intraoperative topical application of papaverine, and cisternal drainage or ventriculocisternal irrigation with or without urokinase after surgery have been attempted to reduce CV.50, 52, 53, 55, 58, 148, 149, 150 With regard to endovascular treatment of CV, balloon angioplasty is performed to dilate the proximal portion of the cerebral arteries, and intraarterial administration of papaverine or fasudil hydrochloride is
Antifibrinolytic Drugs
The use of antifibrinolytic drugs to reduce the risk of rebleeding was shown in 2 studies to have adverse effects on DCI,13, 74 although 3 other groups reported that this had no significant relationship to SV160 or DCI.11, 77 Harrigan et al.42 indicated that short-term treatment with antifibrinolytics might provide protection against rebleeding without associated ischemic complications.
Statins
Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins), which are usually used as
Meta-Analysis
When performing a meta-analysis of the available studies that investigated the risk factors associated with CV after SAH, there are several potential limitations to pooling the data. Study heterogeneity with respect to the definition of CV and methodology is an important factor responsible for variations in results. CV has been defined by various terms; in the present study, only CV defined as SV, CI, DCI, or DIND was adopted as the outcome. It is difficult to perform meta-analysis of all risk
Conclusions
CV after aneurysmal SAH has been defined by various terms, including AV, SV, CI, DCI, and DIND. Considering that the term vasospasm originally meant “vascular narrowing,” AV—diagnosed by assessing the arterial narrowing evident on angiography—should be adopted. Additionally, when the arterial narrowing on angiography was strictly assessed by comparison with control angiograms, AV was observed in >90% of patients with ruptured aneurysms.31, 50, 51, 52, 53, 54, 55, 56, 57, 58 In other words,
References (163)
What are the actual incidence and mortality rates of subarachnoid hemorrhage?
Surg Neurol
(1997)- et al.
Prehemorrhage statin use and the risk of vasospasm after aneurysmal subarachnoid hemorrhage
Surg Neurol
(2009) - et al.
Age-associated vasospasm in aneurysmal subarachnoid hemorrhage
J Stroke Cerebrovasc Dis
(2013) Effect of early operation on cerebral vasospasm
Surg Neurol
(1990)Cerebral vasospasm in elderly patients with ruptured intracranial aneurysms
Surg Neurol
(1991)- et al.
Effect of rapid spontaneous diminution of subarachnoid hemorrhage on cerebral vasospasm
Surg Neurol
(1995) Size of ruptured intracranial saccular aneurysms in patients in Izumo City, Japan
World Neurosurg
(2010)- et al.
Relationship between leukocytosis and ischemic complications following aneurysmal subarachnoid hemorrhage
Surg Neurol
(1987) Trends in incidence and case fatality rates of aneurysmal subarachnoid hemorrhage in Izumo City, Japan, between 1980-1989 and 1990-1998
Stroke
(2001)Trends in surgical and management outcomes in patients with aneurysmal subarachnoid hemorrhage in Izumo City, Japan, between 1980-1989 and 1990-1998
Cerebrovasc Dis
(2005)
Effects of aging on cerebral vasospasm after subarachnoid hemorrhage in rabbits
Stroke
Chronic cerebral vasospasm: effect of calcium antagonists
Neurosurgery
A novel inhibitor of inflammatory cytokine production (CNI-1493) reduces rodent post-hemorrhagic vasospasm
Neurocrit Care
Neutralizing antibody against interleukin-6 attenuates posthemorrhagic vasospasm in the rat femoral artery model
Neurosurgery
Interleukin-6 and development of vasospasm after subarachnoid haemorrhage
Acta Neurochir (Wien)
Role of c-Jun N-terminal kinase in cerebral vasospasm after experimental subarachnoid hemorrhage
Stroke
Hypercholesterolemia increases vasospasm resulting from basilar artery subarachnoid hemorrhage in rabbits which is attenuated by vitamin E
Surg Neurol Int
Prediction of delayed cerebral ischemia, rebleeding, and outcome after aneurysmal subarachnoid hemorrhage
Stroke
Risk factors for cerebral infarction in good-grade patients after aneurysmal subarachnoid hemorrhage and surgery: a prospective study
J Neurosurg
Amount of blood on computed tomography as an independent predictor after aneurysm rupture
Stroke
A statistical analysis of factors related to symptomatic cerebral vasospasm
Acta Neurochir (Wien)
Cigarette smoking-induced increase in the risk of symptomatic vasospasm after aneurysmal subarachnoid hemorrhage
J Neurosurg
Multivariate analysis of predictors of cerebral vasospasm occurrence after aneurysmal subarachnoid hemorrhage
Stroke
Initial loss of consciousness and risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
Stroke
Early identification of patients at risk for symptomatic vasospasm after aneurysmal subarachnoid hemorrhage
Crit Care Med
Effect of cisternal and ventricular blood on risk of delayed cerebral ischemia after subarachnoid hemorrhage: the Fisher scale revisited
Stroke
Factors associated with the development of vasospasm after planned surgical treatment of aneurysmal subarachnoid hemorrhage
J Neurosurg
Leukocytosis as an independent risk factor for cerebral vasospasm following aneurysmal subarachnoid hemorrhage
J Neurosurg
Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid hemorrhage
Crit Care Med
Lower incidence of symptomatic vasospasm after subarachnoid hemorrhage owing to ruptured vertebrobasilar aneurysms
Neurosurgery
Risk of cerebral vasospasm after subarachnoid hemorrhage reduced by statin therapy: a multivariate analysis of an institutional experience
J Neurosurg
Predictors of cerebral infarction in patients with aneurysmal subarachnoid hemorrhage
Neurosurgery
Prediction of angiographic vasospasm after aneurysmal subarachnoid hemorrhage: value of the Hijdra sum scoring system
Neurocrit Care
Predictors of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage: a cardiac focus
Neurocrit Care
Predictors analysis of symptomatic cerebral vasospasm after subarachnoid hemorrhage
Acta Neurochir Suppl
Predicting the lack of development of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
Stroke
Risk factors associated with cerebral vasospasm following aneurysmal subarachnoid hemorrhage
Neurol Med Chir (Tokyo)
Clot volume and clearance rate as independent predictors of vasospasm after aneurysmal subarachnoid hemorrhage
J Neurosurg
Patient age and vasospasm after subarachnoid hemorrhage
Neurosurgery
Serial changes of hemostasis in aneurysmal subarachnoid hemorrhage with special reference to delayed ischemic neurological deficits
J Neurosurg
Effect of rebleeding on the course and incidence of vasospasm after subarachnoid hemorrhage
Neurology
Intraventricular hemorrhage volume predicts poor outcomes but not delayed ischemic neurological deficits among patients with ruptured cerebral aneurysms
Neurosurgery
Evaluation of cerebral vasospasm after early surgical and endovascular treatment of ruptured intracranial aneurysms
Neurosurgery
Symptomatic vasospasm and outcomes following aneurysmal subarachnoid hemorrhage: a comparison between surgical repair and endovascular coil occlusion
J Neurosurg
Does treatment modality of intracranial ruptured aneurysms influence the incidence of cerebral vasospasm and clinical outcome?
Cerebrovasc Dis
Effect of clipping, craniotomy, or intravascular coiling on cerebral vasospasm and patient outcome after aneurysmal subarachnoid hemorrhage
Neurosurgery
Short-term antifibrinolytic therapy before early aneurysm treatment in subarachnoid hemorrhage: effects on rehemorrhage, cerebral ischemia, and hydrocephalus
Neurosurgery
Measuring inconsistency in meta-analyses
BMJ
Investigation of the freely available easy-to-use software “EZR” for medical statistics
Bone Marrow Transplant
Early elevation of serum tumor necrosis factor-α is associated with poor outcome in subarachnoid hemorrhage
J Investig Med
Cited by (83)
Bispectral index monitoring to detect delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage
2022, Journal of Critical CareFactors associated with increased inpatient charges following aneurysmal subarachnoid hemorrhage with vasospasm: A nationwide analysis
2022, Clinical Neurology and Neurosurgery
Conflict of interest statement: The author declares that the article content was composed in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.