Cerebral vasospasm in subarachnoid hemorrhage

Opinion statement The treatment of vasospasm after subarachnoid hemorrhage remains a formidable challenge. The prompt recognition of this complication is essential to prevent ischemic damage. Initial orders should include adequate fluid and sodium supplementation to avoid volume depletion. Prophylactic hypervolemia is not effective in reducing the incidence of vasospasm and may be deleterious. Oral nimodipine (60 mg every 4 hours for 21 days) should be started on admission because it protects against delayed ischemic damage. Increasing blood flow velocities on serial transcranial Doppler studies are reliable indicators of early development of vasospasm. When symptomatic vasospasm occurs, hemodynamic augmentation therapy should be instituted. Crystalloids and colloids may be used to promote hypervolemia. Colloids may provide additional benefit by producing hemodilution. However, the rheological benefits of hemodilution may be offset by reduced oxygen carrying capacity when hematocrit drops below 28%. Hypertension may be induced by administering inotropic drugs and, in certain cases, cardiac output optimization using dobutamine also is necessary. When aggressive medical therapy fails to reverse ischemic deficits, prompt endovascular intervention is indicated. Focal vasospasm of larger vessels may be effectively treated with angioplasty and the benefits of this procedure are durable. Diffuse vasospasm involving smaller arterial branches may be treated with intra-arterial infusion of vasodilators, such as papaverine, verapamil, or nicardipine. Unfortunately, these dilatory effects tend to be short-lasting. In refractory cases, hypothermia may be considered, although value of this strategy remains largely unexplored.     

Cerebral vasospasm after subarachnoid hemorrhage

Cerebral vasospasm causes permanent neurolological deficit or death occurance in 13% of clinical cases. Peak frequency is from 8-10th day after SAH. The purpose of this study is factor analysis that may have influence on vasospasm development , as well as predictor determination. The study is prospective and analysis 192 patients treated in Institute of Neurosurgery, Clinical Centre of Serbia, Belgrade. The majority of patients were admitted in hospital in first four days after SAH, and 184 had GCS over 7. Univariate methods of factor analysis were used, and for significance of predictors influence testing multivariante regression analysis was used. Vasospasm occurred in 22,40% of all cases. No relationships have been found between sex, age, previous hypertension, timing of surgery, appearance of hydrocephalus and intracerebral hematoma, hypertermia or mean arterial blood pressure, with occurrence of cerebral vasospasm. Factors with significantly associated with the occurance of vasospasm were: hearth disease, hypernatriemia, Hct, clinical grade on admission as well as preoperative clinical grade and Fisher CT scan grade. In the first four days after SAH, Fisher scan grade, preoperative clinical grade and Hct, appeared as predictors. After four days, clinical grade on admission and hypernatiemia, showed as poredictors.     

Cerebral vasospasm with subarachnoid hemorrhage from cerebral arteriovenous malformations

The angiograms and clinical records of 12 patients with subarachnoid hemorrhage from cerebral arteriovenous malformations were reviewed. Of these 12 patients, cerebral vasospasm was confirmed in 1 patient. The case of a 28-year-old man who showed angiographic evidence of cerebral vasospasm is reported, and the rarity of vasospasm associated with subarachnoid hemorrhage from cerebral arteriovenous malformations is discussed.     

动脉瘤性蛛网膜下腔出血后脑血管痉挛和围术期容量治疗

背景 动脉瘤破裂蛛网膜下腔出血后脑血管痉挛(cerebral vasospasm,CVS)是一个常见而严重的并发症.CVS造成的继发性脑组织缺血或迟发性脑损伤严重影响患者的预后,是动脉瘤性蛛网膜下腔出血(aneurysm subarachnoid hemorrhage,aSAH)患者伤残和死亡的主要因素. 目的 探究围术期液体治疗和循环容量管理在aSAH后CVS预防和治疗中的有效性,为减少脑动脉瘤手术后CVS发生、改善预后提供参考. 内容 探究动脉瘤破裂蛛网膜下腔出血后CVS病因、病理生理以及如何选择合适的液体进行容量治疗和三高疗法来防治CVS的发生. 趋向 深入研究脑动脉瘤破裂出血后CVS的发病机制和探讨围术期液体治疗以及循环容量管理,为临床防治CVS提供新的思路和方法.     

Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation

Cerebral vasospasm is a common, formidable, and potentially devastating complication in patients who have sustained subarachnoid hemorrhage (SAH). Despite intensive research efforts, cerebral vasospasm remains incompletely understood from both the pathogenic and therapeutic perspectives. At present, no consistently efficacious and ubiquitously applied preventive and therapeutic measures are available in clinical practice. Recently, convincing data have implicated a role of inflammation in the development and maintenance of cerebral vasospasm. A burgeoning (although incomplete) body of evidence suggests that various constituents of the inflammatory response, including adhesion molecules, cytokines, leukocytes, immunoglobulins, and complement, may be critical in the pathogenesis of cerebral vasospasm. Recent studies attempting to dissect the cellular and molecular basis of the inflammatory response accompanying SAH and cerebral vasospasm have provided a promising groundwork for future studies. It is plausible that the inflammatory response may indeed represent a critical common pathway in the pathogenesis of cerebral vasospasm pursuant to SAH. Investigations into the nature of the inflammatory response accompanying SAH are needed to elucidate the precise role(s) of inflammatory events in SAH-induced pathologies.     

N-acetylcysteine prevents vasospasm after subarachnoid hemorrhage

BackgroundThis study investigated the ability of NAC to prevent cerebral vasospasm in a rabbit model of SAH.MethodsTwenty-one, male New Zealand white rabbits were randomly divided into 3 groups of 7 rabbits each: group 1 (control), group 2 (SAH only), group 3 (SAH + NAC treatment). NAC (150 mg/kg, single dose, IP) was administered just before SAH and continued until 72 hours after SAH in group 3.Animals were killed 72 hours after SAH. Tissue MDA levels, SOD, and GSH-Px activities were measured, and basilar artery cross-sectional areas, arterial wall thickness, and endothelial apoptosis in a cross section of basillary artery were determined in all groups.ResultsIntraperitoneal administration of NAC was found to be markedly effective against developing a cerebral vasospasm following a SAH in rabbits. It could significantly reduce elevated lipid peroxidation and increase the level of tissue GSH-Px and SOD enzymatic activities. Also, NAC treatment was found to be effective in increasing the luminal area and reducing wall thickness of the basilar artery. The morphology of arteries in the NAC treatment group was well protected. NAC markedly reduced apoptotic index and protects the endothelial integrity.ConclusionsThis study demonstrates, for the first time, that NAC treatment attenuates cerebral vasospasm in a rabbit SAH model. NAC treatment has significant neuroprotective effect and markedly prevents cerebral vasospasm after SAH. In conclusion, the NAC treatment might be beneficial in preventing cerebral vasospasm after SAH, thus showing potential for clinical implications.     

Diffusion-perfusion mismatch in symptomatic vasospasm after subarachnoid hemorrhage

Diffusion-weighted and perfusion-weighted magnetic resonance (MR) imaging were investigated as a method to detect diffusion-perfusion mismatch in the early stages of vasospasm in 17 patients with acute subarachnoid hemorrhage after aneurysm clipping. Single photon emission computed tomography (SPECT) with N-isopropyl-p-[(123)I]iodoamphetamine was also performed. Diffusion-perfusion mismatch was clearly identified in the 3 patients who manifested clinical deterioration. Perfusion-weighted imaging showed increased mean transit time, normal cerebral blood flow, and increased or normal cerebral blood volume. SPECT revealed no earlier signs of vasospasm. Diffusion-perfusion mismatch was clearly demonstrated in the early stages of vasospasm, so may be useful for early identification of ischemia in vasospasm and initiating appropriate treatment.     

A model for intracranial vasospasm in subarachnoid hemorrhage

Cerebral vasospasm (V.S.P.) is a major complication of subarachnoid hemorrhage. In order to investigate this cerebral vasospasm, an intracisternal injection of autologous blood and topical application around the internal carotid artery was performed in the dog model. Thirty dogs were divided into five groups and a cerebral angiography was performed on D0, D2, D5, D7 and D9. In comparison with the control group (group 1), the angiography in group 2 (12 dogs) systematically exhibited severe V.S.P. In group 3 (intracisternal injection of venous blood: 5 dogs), the angiography exhibited no vasospasm at all. In group 4, a left frontoparietal flap was opened, allowing us to deposit blood around the carotid bifurcation. In these cases, a severe narrowing of cortical arteries was demonstrated. In group 5 (intracisternal injection of heparinated blood), no vasospasm was observed. These findings suggest that the vasospasm involves the circle of Willis' as well as the cortical arteries.     

Cerebral vasospasm evaluated by transcranial ultrasound correlated with clinical grade and CT-visualized subarachnoid hemorrhage

In 39 patients with a proven subarachnoid hemorrhage (SAH), the clinical status, the amount of subarachnoid blood on a computerized tomography scan obtained within 5 days after SAH, and the flow velocities (FV's) in both middle cerebral arteries (MCA's) measured by transcranial Doppler sonography were recorded daily and correlated. All patients had pathological FV's over 80 cm/sec between Day 4 and Day 10 after SAH. The side of the ruptured aneurysm showed higher FV's than did the unaffected side in cases of laterally localized aneurysms. Increase in FV preceded clinical manifestation of ischemia. A step early increase of FV's portended severe ischemia and impending infarction. Maximum FV's in the range of 120 to 140 cm/sec were not critical and in no case led to brain infarction. Maximum FV's over 200 cm/sec were associated with a tendency for ischemia, but the patients may remain clinically asymptomatic. In cases of no or only a little blood in the basal cisterns, mean FV's in both MCA's increased only moderately whereas, with thick clots of subarachnoid blood, there was a steeper and higher increase of mean FV's.     

Magnesium infusion for vasospasm prophylaxis after subarachnoid hemorrhage

OBJECT: Despite the application of current standard therapies, vasospasm continues to result in death or major disability in patients treated for ruptured aneurysms. The authors investigated the effectiveness of continous MgSO4 infusion for vasospasm prophylaxis. METHODS: Seventy-six adults (mean age 54.6 years; 71% women; 92% Caucasian) were included in this comparative matched-cohort study of patients with aneurysmal subarachnoid hemorrhage on the basis of computed tomography (CT) findings. Thirty-eight patients who received continuous MgSO4 infusion were matched for age, race, sex, treatment option, Fisher grade, and Hunt and Hess grade to 38 historical control individuals who did not receive MgSO4infusion. Twelve grams of MgSO4 in 500 ml normal saline was given intravenously daily for 12 days if the patient presented within 48 hours of aneurysm rupture. Vasospasm was diagnosed on the basis of digital substraction angiography, CT angiography, and transcranial Doppler ultrasonography, and evidence of neurological deterioration. Symptomatic vasospasm was present at a significantly lower frequency in patients who received MgSO4 infusion (18%) compared with patients who did not receive MgSO4 (42%) (p = 0.025). There was no significant difference in mortality rate at discharge (p = 0.328). A trend toward improved outcome as measured by the modifed Rankin Scale (p = 0.084), but not the Glasgow Outcome Scale (p = 1.0), was seen in the MgSO4 treated group. CONCLUSIONS: Analysis of the results suggests that MgSO4 infusion may have a role in cerebral vasospasm prophylaxis if therapy is initiated within 48 hours of aneurysm rupture.     

蛛网膜下腔出血后脑血管痉挛的研究进展

脑血管痉挛(cerebral vasospasm,CVS)是蛛网膜下腔出血(subaraachnoid hemorrhage,SAH)后一种常见的灾难性的并发症,其所致迟发性缺血性神经功能损害是造成患者致残和死亡的最主要原因.虽经多年研究,但其发病机制至今尚未完全阐明.一氧化氮、内皮素-1、血红蛋白氧化产物及炎症反应均被认为参与致病过程.针对这些发病机制的治疗措施目前仍处于研究阶段,预期会在今后的脑血管痉挛的防治中发挥重要作用.     

Suramin-induced reversal of chronic cerebral vasospasm in experimental subarachnoid hemorrhage

OBJECT: The naphthylsulfonate derivative suramin is an inhibitor of growth factor receptors (receptor tyrosine kinases) and G protein-coupled P2Y receptors. Both types of these receptors are suspected of being involved in cerebral vasospasm after subarachnoid hemorrhage (SAH). In the current study, the authors examined the therapeutic effects of suramin and a selective P2X-receptor antagonist, pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), in the reversal of vasospasm in an established canine double-hemorrhage model. METHODS: Twenty-four dogs underwent double blood injection into the cisterna magna, with injections given on Days 0 and 2. The dogs were divided randomly into three groups (six animals in each group) to be treated from Days 2 through 6 with the vehicle dimethyl sulfoxide, suramin, or PPADS. An additional group of six dogs received double blood injection without any treatment and served as an SAH control group. The animals were killed on Day 7. Angiography was performed on Day 0 before blood injection and again on Day 7 before the animals were killed. After the death of the animals, the basilar arteries (BAs) were collected for morphological studies and determination of tyrosine kinase expression, and the bloody cerebrospinal fluid (CSF) produced by the hemorrhages was collected for measurement of oxyhemoglobin and adenosine triphosphate (ATP). In the SAH control group, the mean diameter of the BAs on Day 7 was 46.23 +/- 6.32% of the value on Day 0 (which served as a reference of 100%). In the DMSO-treated group, the mean residual diameter of the BA was 47.77 +/- 0.8% on Day 7 compared with the value on Day 0. Suramin, but not PPADS, increased the residual diameter to 74.02 +/- 4.24% on Day 7. On Day 7 the level of ATP in the CSF was decreased and the level of oxyhemoglobin was increased, compared with values measured on Day 0. Suramin, but not PPADS, reduced tyrosine phosphorylation in the spastic BAs. CONCLUSIONS: By reducing tyrosine kinase activity, suramin may be useful in the treatment of cerebral vasospasm.     

Studies of intravascular components in cerebral vasospasm following subarachnoid hemorrhage

Summary Cerebral vasospasm with subsequent infarction gives important influence to the prognosis of patients with ruptured intracranial aneurysms. Many factors should be considered in the pathogenesis of cerebral infarction. Clinical and experimental studies of intravascular components with particular reference to platelet and coagulation factors were performed. Both studies revealed systemic platelet hyperactivity and a hypercoagulable state; in further experimental studies, crenated red blood cells were recognized in the course of cerebral vasospasm. These systemic changes of intravascular components are thought to accelerate cerebral ischemia through formation of microthrombosis, increased blood viscosity and reduced deformability of the red blood cells.This paper was presented in part at the Annual Meeting of the American Association of Neurological Surgeons in Los Angeles in April 1979.