Occurrence Of Symptomatic Vasospasm Research Articles

Hyponatremia as predictor of symptomatic vasospasm in aneurysmal subarachnoid hemorrhage

BackgroundSubarachnoid hemorrhage is one of high morbidity in vascular neurology and neurosurgery and one of the clipart for this is symptomatic vasospasm that can leads to delayed cerebral ischemia. Other common complication is electrolytes and fluid homeostasis disturbance and among these, is Sodium disequilibrium, either hypo- or hypernatremia. In our institution we observed that hyponatremia is common, and it is more evident in patient with symptomatic vasospasm. For that we retrospectively looked at the association of hyponatremia and the occurrence of symptomatic vasospasm or delayed cerebral ischemia in aSAH. MethodsRetrospective chart review with daily monitoring of sodium level from day 1to day 21 from the ictus, aSAH. We include all adult patients (Age > 18 years) who were admitted to intensive care with diagnosis of aSAH and undergone aneurysm securing procedures within 48 h. ResultsAmong 45 patients 24 (43%) developed symptomatic vasospasm and delayed cerebral ischemia and it was most common in males (13/22: 59%). Sodium level especially hyponatremia in period between days (1–4) with median of 134 in vasospasm group (50%). ConclusionsDelayed cerebral ischemia/symptomatic vasospasm occurs more commonly in males and associated with hyponatremia (Na+ <134) and can be predicted in the first 4 days.

Vasospasm-related complications after subarachnoid hemorrhage: the role of patients’ age and sex

Outcome of aneurysmal subarachnoid hemorrhage (SAH) depends strongly on occurrence of symptomatic vasospasm (SV) leading to delayed cerebral ischemia (DCI). Various demographic, radiographic, and clinical predictors of SV have been reported so far, partially with conflicting results. The aim of this study was to analyze the role of patients' age and sex on SV/DCI risk, especially to identify age and sex-specific risk groups. All patients admitted with acute SAH during a 14-year-period ending in 2016 were eligible for this study. The study endpoints were the following: SV requiring spasmolysis, occurrence of DCI in follow-up computed tomography scans and unfavorable outcome at 6months (modified Rankin scale > 2). Nine hundred ninety-four patients were included in this study. The majority was female (666; 67%). SV, DCI, and unfavorable outcomes were observed in 21.5, 21.8, and 43.6% of the patients, respectively. Younger age (p < 0.001; OR = 1.03 per year decrease) and female sex (p = 0.025; OR = 1.510) were confirmed as independent predictors of SV. Regarding the sex differences, there were three age groups for SV/DCI risk ≤ 54, 55-74, and ≥ 75years. Male patients showed earlier decrease in SV risk (at ≥ 55 vs. ≥ 75years in females). Therefore, SAH females aged between 55 and 74years were at the highest risk for DCI and unfavorable outcome, as compared to younger/older females (p = 0.001, OR = 1.77/p = 0.001, OR = 1.80). In contrast, their male counterparts did not show these risk alterations (p = 0.445/p = 0.822). After acute SAH, female and male patients seem to show different age patterns for the risk of SV and DCI. Females aged between 55 and 74years are at particular risk of vasospasm-related SAH complications, possibly due to onset of menopause. DRKS, Unique identifier: DRKS00008749.

Effect of Cilostazol on Cerebral Vasospasm and Outcome in Patients with Aneurysmal Subarachnoid Hemorrhage: A Randomized, Double-Blind, Placebo-Controlled Trial

Background: Several clinical studies have indicated the efficacy of cilostazol, a selective inhibitor of phosphodiesterase 3, in preventing cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH). They were not double-blinded trial resulting in disunited results on assessment of end points among the studies. The randomized, double-blind, placebo-controlled study was performed to assess the effectiveness of cilostazol on cerebral vasospasm. Methods: Patients with aneurysmal SAH admitted within 24 h after the ictus who met the following criteria were enrolled in this study: SAH on CT scan was diffuse thick, diffuse thin, or local thick, Hunt and Hess score was less than 4, administration of cilostazol or placebo could be started within 48 h of SAH. Patients were randomly allocated to placebo or cilostazol after repair of a ruptured saccular aneurysm by aneurysmal neck clipping or endovascular coiling, and the administration of cilostazol or placebo was continued up to 14 days after initiation of treatment. The primary end point was the occurrence of symptomatic vasospasm (sVS), and secondary end points were angiographic vasospasm (aVS) evaluated on digital subtraction angiography, vasospasm-related new cerebral infarction evaluated on CT scan or MRI, and clinical outcome at 3 months of SAH as assessed by Glasgow Outcome Scale, in which poor outcome was defined as severe disability, vegetative state, and death. All end points were evaluated with blinded assessment. Results: One hundred forty eight patients were randomly allocated to the cilostazol group (n = 74) or the control group (n = 74). The occurrence of sVS was significantly lower in the cilostazol group than in the control group (10.8 vs. 24.3%, p = 0.031), and multiple logistic analysis showed that cilostazol use was an independent factor reducing sVS (OR 0.293, 95% CI 0.099-0.568, p = 0.027). The incidence of aVS and vasospasm-related cerebral infarction were not significantly different between the groups. Poor outcome was significantly lower in the cilostazol group than in the control group (5.4 vs. 17.6%, p = 0.011), and multiple logistic analyses demonstrated that cilostazol use was an independent factor that reduced the incidence of poor outcome (OR 0.221, 95% CI 0.054-0.903, p = 0.035). Severe adverse events due to cilostazol administration did not occur during the study period. Conclusions: Cilostazol administration is effective in preventing sVS and improving outcomes without severe adverse events. A larger-scale study including more cases was necessary to confirm this efficacy of cilostazol.

High-Dose Simvastatin Is Effective in Preventing Cerebral Vasospasm after Aneurysmal Subarachnoid Hemorrhage: A Prospective Cohort Study in Korean Patients.

ObjectiveThe goal of this study was to assess the effect of high-dose simvastatin on cerebral vasospasm and its clinical outcome after aneurysmal subarachnoid hemorrhage (SAH) in Korean patients.MethodsThis study was designed as a prospective observational cohort study. Its subjects were aneurysmal SAH patients who had undergone aneurysm clipping or coiling. They were assigned to 1 of 3 groups : the 20 mg, 40 mg, and 80 mg simvastatin groups. The primary end-point was the occurrence of symptomatic vasospasm. The clinical outcome was assessed with the modified Rankin Scale (mRS) score after 1 month and 3 months. The risk factors of the development of vasospasm were assessed by logistic regression analysis.ResultsNinety nine patients with aneurysmal SAH were treated and screened. They were sequentially assigned to the 20 mg (n=22), 40 mg (n=34), and 80 mg (n=31) simvastatin groups. Symptomatic vasospasm occurred in 36.4% of the 20 mg group, 8.8% of the 40 mg group, and 3.2% of the 80 mg group (p=0.003). The multiple logistic regression analysis showed that poor Hunt-Hess grades (OR=5.4 and 95% CI=1.09-26.62) and high-dose (80 mg) simvastatin (OR=0.09 and 95% CI=0.1-0.85) were independent factors of symptomatic vasospasm. The clinical outcomes did not show a significant difference among the three groups.ConclusionThis study demonstrated that 80 mg simvastatin treatment was effective in preventing cerebral vasospasm after aneurysmal SAH, but did not improve the clinical outcome in Korean patients.

Transfer Time to a High-volume Center for Patients with Subarachnoid Hemorrhage Does Not Affect Outcomes

The objective of our study was to examine patients with aneurysmal subarachnoid hemorrhage transferred and directly admitted to our institution in order to determine how transfer time affects outcomes. A retrospective cohort study was performed of all patients undergoing treatment for aneurysmal subarachnoid hemorrhage between 2005 and 2012 at the University of Michigan. Variables, including transfer time, were tested for their independent association with the primary outcomes of symptomatic vasospasm and 12-month outcome as well as secondary outcomes of aneurysm rebleeding and 12-month mortality. During the study period, 263 (87.4%) patients were transferred to our institution and 38 (12.6%) were directly admitted for treatment of aneurysmal subarachnoid hemorrhage. Transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. Higher Hunt-Hess grade was associated with the occurrence of symptomatic vasospasm as well as with poorer 12-month outcome. Transfer time was not associated with the occurrence of symptomatic vasospasm, 12-month outcome, rebleeding, or 12-month mortality. We believe our data argue that protocols should emphasize early resuscitation and stabilization followed by safe transfer rather than a hyperacute transfer paradigm. However, transfer time should be minimized as much as possible so as not to delay time to definitive treatment.

Changes in the Cerebrospinal Fluid Ceramide Profile After Subarachnoid Hemorrhage

The purpose of this study was to investigate changes in the cerebrospinal fluid sphingolipid profile in patients with subarachnoid hemorrhage in relation to the occurrence of symptomatic vasospasm and outcome at hospital discharge. The ceramide profile in the cerebrospinal fluid was determined by mass spectrometry in control subjects and patients with Fisher 3 grade subarachnoid hemorrhage within 48 hours of the bleed. Patients were prospectively followed and subcategorized based on the occurrence of symptomatic vasospasm and modified Rankin Scale at discharge. Compared to control subjects, patients with subarachnoid hemorrhage had higher cerebrospinal fluid levels of total ceramide (12.4±8.8 versus 54.6±49.3 pmol/mL; P<0.001). In the subgroup analysis, total ceramide levels in individuals with symptomatic vasospasm (104.2±57.0 pmol/mL) were higher than in those with asymptomatic vasospasm (32.4±25.7 pmol/mL; P=0.006) and no vasospasm (30.9±15.7 pmol/mL; P=0.003). In addition, compared to patients with a good outcome (modified Rankin Scale ≤3), individuals with poor outcome (modified Rankin Scale ≥4) had higher cerebrospinal fluid levels of total ceramide (79±25 versus 23±6 pmol/mL; P=0.008). When the relative contributions of the different ceramide species were calculated, a higher relative concentration of C(18:0) ceramide was observed in individuals with symptomatic vasospasm (P=0.018) and poor outcome (P=0.028). Ceramide profile changes occur in subarachnoid hemorrhage. In this small case-based series elevation of levels of this sphingolipid, particularly C(18:0), was associated with the occurrence of symptomatic vasospasm and poor neurological outcome after subarachnoid hemorrhage.

Quantification of Subarachnoid Hemorrhage by Three-Dimensional Computed Tomography: Correlation Between Hematoma Volume and Symptomatic Vasospasm

Subarachnoid hemorrhage (SAH) volume was measured by three-dimensional computed tomography (3D-CT) and the correlation examined between the SAH volume and the occurrence of symptomatic vasospasm (SVS). Experimental (in vitro) hematomas were made with blood obtained from 10 volunteers. The hematoma volume was determined by actual measurements and by 3D-CT using a CT number in the range of 40-80 Hounsfield units (HU) on days 1, 4, 7, 11, and 14. The coefficients on days 1 and 4 were relatively high and the correlation between measured and estimated volumes was significant on days 7, 11, and 14. 3D-CT was also performed in 50 patients with SAH at onset (day 0) and on days 1, 4, 7, and 14. The hematoma volume including the volume of normal structures was automatically calculated (V1). The volume of normal structures (V2) with CT numbers of 40-80 HU was calculated in another 50 patients without intracranial lesions as 12 ml. The total hematoma volume was defined as V1 minus mean V2. The mean SAH volume was 44, 36, 21, 11, and 8 ml on days 0, 1, 4, 7, and 14, respectively. The hematoma volumes were significantly larger in patients with SVS than in patients without SVS at all time points. The minimum hematoma volume in patients with SVS was 92, 76, 42, 24, and 12 ml on days 0, 1, 4, 7, and 14, respectively. This method allows the quantitative determination of SAH volume based on 3D-CT, and may be useful in clinical studies of cerebral vasospasm.

Does eicosapentaenoic acid (EPA) inhibit cerebral vasospasm in patients after aneurysmal subarachnoid hemorrhage?

Cerebral vasospasm following subarachnoid hemorrhage (SAH) is a significant cause of morbidity and mortality and recent studies indicate that Rho-kinase plays an important role in the occurrence of such cerebral vasospasm. Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid, inhibits sphingosylphosphorylcholine (SPC)-induced Rho-kinase activation in vitro, so this study examined whether EPA prevented cerebral vasospasm occurrence after SAH in patients. The trial population was 101 patients with SAH subjected to craniotomy and clip application. EPA was orally administered at a daily dose of 1800 mg EPA from day 4 to day 14 to 73 patients; the other 28 constituted the control group, receiving no EPA. EPA significantly curtailed both the occurrence of symptomatic vasospasm (14% EPA group, 36% control, P = 0.019) and of cerebral infarction because of cerebral vasospasm (4% EPA group, 29% control, P = 0.001). Moreover, the percentage of patients with a clinically good outcome was significantly higher in the EPA group (85%, P = 0.022) than in control (64%); there were no deaths in the EPA group but three (11%) in control (P = 0.020). These findings suggest EPA inhibits symptomatic cerebral vasospasm and cerebral infarction after SAH and also improves clinical prognosis.

Effect of arachnoid plasty using fibrin glue membrane after clipping of ruptured aneurysm on the occurrence of complications and outcome in the elderly patients

In elderly patients with aneurysmal subarachnoid hemorrhage (SAH), complications including vasosopasm, subdural effusion, and late hydrocephalus, are liable to occur even after aneurysmal surgery. We examined prospectively the efficacy of arachnoid plasty using fibrin glue membrane during surgery of ruptured aneurysms in the elderly patients for preventing complications. The effects on the modified Rankin scale (mRS) and the Glasgow outcome scale (GOS) 3 months after SAH were noted. Total of 31 patients aged more than 70 years selected from a consecutive series of patients with aneurysmal SAH, were divided into two groups alternately, a group with arachnoid plasty (n = 16) and a control group without arachnoid plasty (n = 15). Statistical analyses were performed to assess relationships among various clinical and neuroradiological variables, especially between arachnoid plasty and occurrence of symptomatic vasospasm, subdural effusion, late hydrocephalus, or outcome such as mRS and GOS 3 months after onset. Statistical analyses revealed that arachnoid plasty were associated with late hydrocephalus and subdural effusion negatively, but with better mRS at 3 months after SAH. A tendency to be associated with less frequent symptomatic vasospasm was also noted. Arachnoid plasty using fibrin glue is suggested to be effective in preventing complications associated with SAH and aneurysmal surgery. A better outcome in the elderly patients can be achieved.

Lower Incidence of Symptomatic Vasospasm after Subarachnoid Hemorrhage owing to Ruptured Vertebrobasilar Aneurysms

In this study, we evaluated the difference in incidence of symptomatic vasospasm between ruptured aneurysms in the anterior and posterior circulation using multiple logistic regression analysis. A total of 145 consecutive patients who underwent surgery for aneurysms within 72 hours after subarachnoid hemorrhage (SAH) were studied. The ruptured aneurysm was in the anterior circulation in 128 patients (88.3%) and in the posterior circulation in 17 patients (11.7%). Forty patients (27.6%) had symptomatic vasospasm and 105 patients (72.4%) did not. Univariate and multivariate analyses were performed to assess relationships among various variables and the occurrence of symptomatic vasospasm after SAH. Finally, Grade III to V (Hunt and Hess grade) and Group 3 (Fisher's classification) on admission were found to be independently positively associated with the occurrence of symptomatic vasospasm while ruptured vertebrobasilar aneurysm were negatively associated. Although a poor clinical grade and a severe SAH classification on admission such as Hunt and Hess grade and Fisher's classification are established powerful predictors of symptomatic vasospasm, ruptured vertebrobasilar aneurysm are for the first time reported to be a predictor of symptomatic vasospasm based on results of a recent reliable statistical analysis.

Relationship between hyperglycemia and symptomatic vasospasm after subarachnoid hemorrhage*

To determine the relationship between blood glucose levels (mg/dL) and occurrence of symptomatic vasospasm (VSP) and clinical outcomes after aneurysmal subarachnoid hemorrhage. Retrospective observational study of 352 patients with subarachnoid hemorrhage admitted within 48 hrs of ictus between January 1995 and June 2002. Neurointensive care unit. Adult patients admitted after subarachnoid hemorrhage. None. Variables included age; Hunt-Hess classification score; Fisher group; insulin use; infectious disease status; history of diabetes mellitus; and blood glucose values. Poor clinical outcome was defined by a modified Rankin score > or =3, and hyperglycemia was defined by a blood glucose level >140 mg/dL. Mean daily blood glucose values were assessed from admission to development of VSP or day 14. Mean admission blood glucose value, mean inpatient blood glucose value, insulin use, infectious disease status, Hunt-Hess classification score, Fisher group, and history of diabetes mellitus were entered in a Cox proportional hazards model. VSP occurred in 103 (29.2%) of 352 patients. Mean admission blood glucose values (176.6 +/- 40.3 mg/dL vs. 162.3 +/- 47.8 mg/dL; p = .01) and mean inpatient blood glucose values (166.2 +/- 24.7 mg/dL vs. 155.8 +/- 29.7 mg/dL; p = .001) were significantly higher in patients with VSP. Mean inpatient blood glucose value (relative risk, 1.01; 95% confidence interval, 1.0-1.03; p = .04), Hunt-Hess classification score > or =3 (relative risk, 2.23; 95% confidence interval, 1.21-3.99; p = .02), and Fisher group score of 3 (relative risk, 1.28; 95% confidence interval, 1.15-3.1; p = .05) increased the risk for VSP. Hyperglycemia was associated with longer length of stay in the neurointensive care unit (14.5 +/- 7.1 days vs. 11.6 +/- 5.4 days; p < .001) and poor outcome at discharge (modified Rankin score > or =3: 58.9% vs. 18.8%; p < .001). Mean inpatient blood glucose value is associated with the development of VSP and may represent a target for therapy to prevent VSP and improve clinical outcomes.

Postoperative anticonvulsant prophylaxis for patients treated for cerebral aneurysms.

The incidences of postoperative seizures and side effects were evaluated in 193 patients with cerebral aneurysm who received anticonvulsant prophylaxis and underwent 224 craniotomies for cerebral aneurysms between 1993 and 1995. The patients were 73 males and 120 females aged between 31 and 80 years. One hundred and sixteen patients had ruptured cerebral aneurysms and 108 had unruptured aneurysms. Phenytoin followed by valproic acid were administered. Early postoperative seizures occurred in five patients (4 with ruptured and 1 with unruptured aneurysms) within 14 days after surgery. Late postoperative seizures occurred in four different patients with ruptured aneurysms more than 14 days after surgery. The presence of cortical lesions detected by cerebral computed tomography and occurrence of symptomatic vasospasm were correlated with the occurrence of early postoperative seizure (p < 0.05). Three of the four patients with late postoperative seizure had cortical lesions and two were receiving continued medication. Side effects that warranted discontinuation of therapy were seen in the follow-up period in 12.9% of patients. Anticonvulsant prophylaxis is not recommended due to the higher incidence of side effects than seizure, except in patients in poor clinical condition for the purpose of brain protection. Otherwise, anticonvulsant medication should be initiated at the time of the initial seizure attack.

Cisternal CSF levels of cytokines after subarachnoid hemorrhage

Cytokines are considered as mediators of immune and inflammatory responses. Cisternal CSF levels of interleukin (IL)-6, IL-8, monocyte chemoattractant protein-1 (MCP-l) and of the soluble adhesion molecule E-selectin were evaluated in patients operated on for intracranial aneurysms. Cisternal CSF samples were obtained at surgery in 41 selected patients (31 with diagnosis of subarachnoid hemorrhage (SAH) and 10 control patients operated on for incidental unruptured aneurysms); 14 patients were operated within 72 h after SAH (early surgery) and 17 were operated after day 10 after the hemorrhage (delayed surgery). The CSF levels of cytokines were evaluated using radioimmunoassay and their concentrations were related to the timing of surgery, the amount of cisternal subarachnoid blood clots and the onset of clinical and angiographical evidence of arterial vasospasm. Mean cisternal CSF levels of IL-6I IL-8 and AMCP-1 are significantly higher in samples obtained from patients early operated after SAH, while levels of E-selectin were below the threshold value of the method in all 41 cases. In the early operated group 7 patients presented symptomatic vasospasm: levels of IL-8 and MCP-1 were not significantly different when compared to those of uncomplicated cases; on the other hand, significantly higher levels of IL-6 were shown in the subgroup of patients operated within 72 h after SAH and developing vasospasm. Among the patients undergoing delayed surgery 5 presented symptomatic vasospasm, but no significant difference was shown in cisternal CSF levels ofcytokines measured. The results of the present study show that in patients with unruptured aneurysms cytokines are present in cisternal CSF in scarce quantities and that in subarachnoid spaces after SAH there is an impressive increase of IL-6, IL-8 and MCP-l. MoreoverL the higher cisternal CSF levels of IL-6 found in the early stage after SAH might have a predictive value regarding the occurrence of symptomatic vasospasm. [Neural Res 1998; 20: 337-342]

Combination Therapy of Fasudil Hydrochloride and Ozagrel Sodium for Cerebral Vasospasm Following Aneurysmal Subarachnoid Hemorrhage

Fasudil hydrochloride is a new type of intracellular calcium antagonist, different from the calcium entry blockers that are commonly employed for clinical use. Since September 1995, the combination of fasudil hydrochloride and ozagrel sodium, an inhibitor of thromboxane A2 synthesis, has been used to treat 60 patients at risk of cerebral vasospasm after aneurysmal subarachnoid hemorrhage. The effectiveness of this combination therapy was investigated by comparison with the outcome of 57 patients previously treated with only ozagrel sodium. The combination therapy was significantly more effective (p < 0.01) in reducing the incidence of low density areas on computed tomography scans, and reduced, but not significantly, the occurrence of symptomatic vasospasm. The combination therapy of fasudil hydrochloride and ozagrel sodium has superior effectiveness over only ozagrel sodium in treating patients at risk of vasospasm after aneurysmal subarachnoid hemorrhage.

Anti-phospholipid antibodies and cerebral vasospasm following subarachnoid haemorrhage.

Delayed ischaemic deficits due to cerebral vasospasm contribute to the high morbidity and mortality rates associated with subarachnoid haemorrhage. We evaluated the usefulness of measuring anti-phospholipid antibodies (aPLs) for prediction of the occurrence of symptomatic vasospasm and the outcome after subarachnoid haemorrhage. 32 consecutive patients with subarachnoid haemorrhage due to ruptured cerebral aneurysms were studied. They were admitted and operated on within 72 hours after the onset of subarachnoid haemorrhage. aPLs such as lupus anticoagulants, anti-cardiolipin IgG and anti-cardiolipin IgM were measured repeatedly after admission. Furthermore, platelet count, platelet aggregability and plasma platelet factor 4 were also measured. Eleven among the 32 patients (34.4%) showed positive in the examination for aPLs. Although aPLs could not predict symptomatic vasospasm, once symptomatic vasospasm occurred, patients with aPLs frequently demonstrated cerebral infarction and therefore their outcome was worse. aPLs were associated with a severe initial clinical grade and SAH grade on CT scan. Therefore it may explain the association of aPLs with worse outcome. aPLs were detected between 1 and 7 days. Four of 6 patients (67%) with aPLs became negative between 7 and 13 days after subarachnoid haemorrhage. The mechanism of transient aPLs is unclear but it is more likely to occur in the severer grade patients. The reduction in platelet count, the increased platelet aggregability, and the increased plasma platelet factor 4 concentration were also observed in aPLs-positive patients with symptomatic vasospasm.