Serum and cerebrospinal fluid C-reactive protein levels as predictors of vasospasm in aneurysmal subarachnoid hemorrhage

Clinical article

Full access

Object

Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. The Creactive protein (CRP) constitutes a highly sensitive inflammatory marker. The association of elevated systemic CRP and coronary vasospasm has been well established. Additionally, elevation of the serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between elevated CRP levels in the serum and CSF and the development of vasospasm in patients with aSAH.

Methods

. A total of 41 adult patients in whom aSAH was diagnosed were included in the study. Their demographics, the admitting Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum and CSF CRP measurements were obtained on Days 0, 1, 2, 3, 5, 7, and 9. All patients underwent either surgical or endovascular treatment within 48 hours of their admission. The outcome was evaluated using the Glasgow Outcome Scale and the modified Rankin Scale.

Results

The CRP levels in serum and CSF peaked on the 3rd postadmission day, and the CRP levels in CSF were always higher than the serum levels. Patients with lower admission GCS scores and higher Hunt and Hess and Fisher grades had statistically significantly higher levels of CRP in serum and CSF. Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort.

Conclusions

Patients with aSAH who had high Hunt and Hess and Fisher grades and low GCS scores showed elevated CRP levels in their CSF and serum. Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort.

Abbreviations used in this paper:aSAH = aneurysmal subarachnoid hemorrhage; CRP = C-reactive protein; DIND = delayed ischemic neurological deficit; DS = digital subtraction; GCS = Glasgow Coma Scale; GOS = Glasgow Outcome Scale; IL = interleukin; mRS = modified Rankin Scale.

Abstract

Object

Cerebral vasospasm is a common and potentially devastating complication of aneurysmal subarachnoid hemorrhage (aSAH). Inflammatory processes seem to play a major role in the pathogenesis of vasospasm. The Creactive protein (CRP) constitutes a highly sensitive inflammatory marker. The association of elevated systemic CRP and coronary vasospasm has been well established. Additionally, elevation of the serum CRP levels has been demonstrated in patients with aSAH. The purpose of the current study was to evaluate the possible relationship between elevated CRP levels in the serum and CSF and the development of vasospasm in patients with aSAH.

Methods

. A total of 41 adult patients in whom aSAH was diagnosed were included in the study. Their demographics, the admitting Glasgow Coma Scale (GCS) score, Hunt and Hess grade, Fisher grade, CT scans, digital subtraction angiography studies, and daily neurological examinations were recorded. Serial serum and CSF CRP measurements were obtained on Days 0, 1, 2, 3, 5, 7, and 9. All patients underwent either surgical or endovascular treatment within 48 hours of their admission. The outcome was evaluated using the Glasgow Outcome Scale and the modified Rankin Scale.

Results

The CRP levels in serum and CSF peaked on the 3rd postadmission day, and the CRP levels in CSF were always higher than the serum levels. Patients with lower admission GCS scores and higher Hunt and Hess and Fisher grades had statistically significantly higher levels of CRP in serum and CSF. Patients with angiographic vasospasm had higher CRP measurements in serum and CSF, in a statistically significant fashion (p < 0.0001). Additionally, patients with higher CRP levels in serum and CSF had less favorable outcome in this cohort.

Conclusions

Patients with aSAH who had high Hunt and Hess and Fisher grades and low GCS scores showed elevated CRP levels in their CSF and serum. Furthermore, patients developing angiographically proven vasospasm demonstrated significantly elevated CRP levels in serum and CSF, and increased CRP measurements were strongly associated with poor clinical outcome in this cohort.

Aneurysmal subarachnoid hemorrhage constitutes a devastating and complicated clinical entity. Despite the recent advances in its early detection, diagnosis, and its proper treatment, the overall outcome of patients with aSAH remains poor.11,58 Approximately 50% of patients suffering aSAH will die, 15% of them will become severely disabled, and only 20–35% will return to normal life and activities.11,15,43,58

Cerebral vasospasm remains the most troublesome complication of aSAH. It is associated with high morbidity and mortality rates, even after successfully treating the ruptured aneurysm. The occurrence of cerebral vasospasm varies significantly. It has been demonstrated to be as high as 70% based on angiographic findings, and in 20–30% of patients, vasospasm is responsible for the development of a DIND.15,23,29

Several theories have been proposed in an attempt to explain the underlying pathophysiological mechanisms of cerebral vasospasm.7,17,18,37,53,65 However, none of the proposed theories has been experimentally proven, and the underlying mechanism causing this complex problem remains unknown. Among these theories, a relatively recent one postulates that an inflammation-based pathogenetic mechanism is implicated in the development of coronary vasospasm.11,55 Previous experimental and clinical studies have demonstrated that inflammatory changes occur in spastic coronary arteries.4,19,25,26,61,65 It has been demonstrated that eosinophilic cell counts and plasma fibrinogen levels could predict the severity of vasospastic angina pectoris.65 Additionally, previous clinical studies have shown that elevated levels of high-sensitivity CRP could predict the development of coronary vasospasm.26 The measurement of sensitive inflammatory markers such as CRP significantly increases our ability to predict with accuracy and possibly to prevent or appropriately treat coronary thrombotic events.4,19,25,26,61,65 Furthermore, elevated CRP is associated with increased risk of a subsequent myocardial infarction.

A similar inflammatory response affecting the cerebral vasculature is elicited in cases of aSAH via the release of various cytokines such as IL-6, IL-1, and tumor necrosis factor; increased leukocyte trafficking; and macrophage and complement cascade activation.11,55 Additionally, it has been demonstrated that CRP, an acute-phase protein, which is a highly sensitive indicator of inflammatory response, is produced by hepatocytes in response to increased production of IL-6.6,44,63 Because IL-6 has been associated with the development of cerebral vasospasm, increased levels of CRP at the time of the patients' admissions and early in their postictal courses might have some predictive value in the early detection and proper management of vasospasm.

In our current study, we present our results from measuring the CRP levels in the serum and CSF of patients suffering aSAH, and we explore the relationship of systemic and CSF CRP levels and the development of cerebral vasospasm.

Methods

Our prospective clinical study was approved by the institutional review boards of the participating institutions, and the collection and analysis of all data were performed according to the current Health Insurance Portability and Accountability Act regulations. A detailed written consent form was obtained from all participants or from their legal representatives or next of kin in those cases in which the patient was unable to consent. The inclusion criteria of our study were as follows: 1) diagnosis of aSAH established by a CT scan and a subsequent 4-vessel DS angiography study; 2) patient age > 18 years; 3) patient admission to our institutions within the first 24 hours postictus; 4) patient's surgical or endovascular treatment within 48 hours from admission to our hospitals; 5) pre- and posttreatment DS angiography for vasospasm documentation purposes; and 6) external ventriculostomy insertion. Patients with concomitant or recent acute myocardial infection, history of recent (≤ 30 days) surgery prior to the ictal event, and/or clinical or laboratory evidence of chronic systemic infection were excluded from our study. In addition, patients who received no external ventriculostomy or who died before completing 10 days of treatment were excluded from our current study.

The study covered a 4-year period (2004–2007). A total of 286 patients was admitted during this period with an established diagnosis of aSAH. However, only 41 patients met our inclusion criteria and participated in our study. There were 25 men and 16 women, with a mean age of 51.8 years and ages ranging between 34 and 72 years. A total of 46 aneurysms were identified in our cohort.

The participants' demographic data, their admission GCS scores, Hunt and Hess grades, and Fisher grades, their detailed daily neurological examinations, and their head CT scans were recorded. A standard 4-vessel DS angiography study was obtained on admission in all patients, and another DS angiography was obtained between the 7th and 10th posttreatment day. An intraoperative DS angiography study was performed in 28 (68.3%) of our 41 patients. An external ventriculostomy was made in all participants ipsilaterally to the blood clot if there were any intraventricular clots, or in the right lateral ventricle in cases with no intraventricular hemorrhage or symmetrical intraventricular hemorrhage. The ventricular catheter was tunneled under the skin and was routinely externalized 2.5–3 cm away from the entry site. Surgical clipping was performed in 33 (80.5%) of the 41 patients for 35 (76.1%) of the 46 aneurysms, whereas endovascular treatment was used in 8 (19.5%) of the 41 patients for 11 (23.9%) of the 46 aneurysms. The selection of surgical versus endovascular treatment was based on criteria such as the anatomical location of the lesion, the size and morphological features of the aneurysm, the presence of multiple aneurysms, the presence of mass effect caused by the aneurysm and/or an associated hematoma, the patient's neurological and general medical condition, and the patient's preference. It has to be emphasized that either surgical or endovascular treatment was performed within 48 hours of patient admission.

The CRP level in serum and CSF was measured in each patient on Days 0 (on admission to our centers), 1, 2, 3, 5, 7, and 9, and the measurements obtained were recorded. Blood serum specimens were collected from an inserted venous line, whereas the CSF specimens were collected through an external ventriculostomy. The CRP levels were measured using a nephelometric methodology. All the CRP measurements were expressed as milligrams/liter. The mean serum and CSF values were calculated for each participant.

The patients' clinical outcome was evaluated using the GOS and mRS at discharge from our institutions, and all participants' scores were recorded.

Results

The anatomical location of the lesions and the preoperatively measured maximum diameter of the aneurysmal dome in our cohort are summarized in Tables 1 and 2, respectively. The admission GCS scores ranged between 4 and 15 (mean 11.7). The Hunt and Hess scores on admission ranged between I and V (mean 2.5), and the Fisher grades in our patients ranged between 1 and 4 (mean 1.9). The GOS scores on discharge ranged between 2 and 5 (mean 4.3), and the range of mRS scores was 0–5 (mean 1.1). Analytical data obtained in our patients are summarized in Table 3.

TABLE 1:

Anatomical location of 46 treated aneurysms in 41 patients with aSAH

Location of LesionNo. of Aneurysms
posterior communicating artery14
anterior communicating artery11
middle cerebral artery7
internal carotid artery5
basilar artery5
anterior choroidal artery2
posterior inferior cerebellar artery2
TABLE 2:

Number of aneurysms with small, large, or giant domes in 41 patients with aSAH

Max Diameter of Aneurysmal Dome*No. of Aneurysms
<10 mm9
10–25 mm31
>25 mm6

The dome's largest diameter was measured on the preoperative DS angiography study.

TABLE 3:

Demographic data, neurological grades on admission, postoperative findings, and scores at discharge in 41 patients with aSAH*

Case No.Age (yrs), SexGCS ScoreH & H GradeFisher GradeVasospasm on Postop DSAGOS ScoremRS Score
154, M15II1+50
246, M15I150
369, F9III3+42
472, M12II2+50
539, F14I1+50
645, M15I150
751, F6IV4+34
862, M13II350
944, M5I150
1059, F12III3+42
1162, M15II150
1240, M8IV3+42
1358, F14II150
1435, F15I150
1568, M9III2+42
1655, M14II142
1746, M12III2+51
1865, F15I150
1940, F15I150
2057, M13II151
2161, M8IV242
2265, M15I150
2359, M7IV334
2460, F14II150
2545, M13II150
2639, F12III2+42
2742, M6V434
2834, M8IV3+34
2961, F15I150
3054, M7III3+42
3147, M4V4+25
3258, M15I150
3347, F12II2+50
3438, F13III2+50
3541, F5V425
3666, M15I150
3745, F11III342
3854, M13II250
3938, M9IV350
4044, F10II350
4160, M14II150

DSA = digital subtraction angiography; H & H = Hunt & Hess; + = present; - = absent.

In regard to the measured CRP levels, there was a progressive increase in the CRP levels from the admission to the 3rd postadmission day (3rd or 4th postictal day), which was followed by a slow decrease toward the 9th postadmission day (Fig. 1). There was a parallel course of increase in the CRP levels in CSF and serum. The observed CRP levels in the CSF were significantly higher than the levels of CRP in the serum throughout the entire postictal period (paired t-test methodology; t = 6.547, p < 0.0001) (Fig. 1).

Fig. 1.
Fig. 1.

Schematic representation of summated measured CRP levels in the serum and CSF of our patients.

Angiographic vasospasm was detected in 15 (36.6%) of our 41 patients in the DS angiography studies obtained posttreatment. Analysis of our angiographic data demonstrated that there was a regional pattern of vasospasm, affecting mainly the parent and adjacent vessels in 9 (21.9%) of our 41 patients, whereas in 6 (14.6%) of 41, global vasospasm was evident. Interestingly, clinical symptoms caused by the observed cerebral vasospasm developed in 8 (19.5%) of 41 patients in our cohort. These symptoms were managed solely medically in 6 cases, whereas in the remaining 2 cases intravascular balloon angioplasty was necessary.

Statistical analysis of our data showed that patients developing angiographic vasospasm in our cohort had higher CRP levels in serum (Fig. 2 upper). This difference reached the level of statistical significance (unpaired t-test methodology; df = 39, t = −4.678, p < 0.0001). Similarly, patients with angiographically proven vasospasm demonstrated higher CRP levels in CSF, in a statistically significant fashion (unpaired t-test methodology; df = 39, t = −4.201, p < 0.0001) (Fig. 2 lower). On the contrary, the difference in occurrence of angiographic vasospasm between patients undergoing surgical clipping and those undergoing endovascular coil insertion was not statistically significant (chi-square statistical methodology; χ2 = 0.004, df = 1, p = 0.95). The strength of our last statistical analysis is very limited, however, due to the small number of participants in the endovascular group.

Fig. 2.
Fig. 2.

Upper: Schematic representation of CRP levels in serum in patients with and without vasospasm. Lower: Schematic representation of CRP levels in CSF in patients with and without vasospasm.

In regard to the admission GCS score and the serum CRP levels, we found that patients with lower GCS scores had increased CRP measurements in serum (correlation coefficient methodology; z = −8.139, p < 0.0001, r = −0.87) (Fig. 3 upper) and CSF (z = −6.443, p < 0.0001, r = −0.78) (Fig. 3 lower). Low admission GCS scores were significantly inversely correlated with high CRP values in serum and CSF. Likewise, patients with higher Hunt and Hess grades on admission developed significantly higher CRP levels in serum (correlation coefficient methodology; z = 6.244, p < 0.0001, r = 0.77) and CSF (z = 5.850, p < 0.0001, r = 0.74). Similarly, patients with higher admission Fisher grades showed increased levels of CRP in serum (correlation coefficient methodology; z = 7.132, p < 0.0001, r = 0.82) and CSF (z = 6.700, p < 0.0001, r = 0.80).

Fig. 3.
Fig. 3.

Upper: Schematic representation of CRP levels in serum with regard to the admission GCS score. Lower: Schematic representation of CRP levels in CSF with regard to the admission GCS score.

There was no statistically significant difference in the serum CRP levels between the group of patients undergoing surgical clipping and those undergoing endovascular coil occlusion, although the surgical group had higher serum CRP levels (unpaired t-test methodology; t = 1.151, p = 0.2569) (Fig. 4 upper). Likewise, the CRP differences in CSF between these 2 groups did not reach levels of statistical significance (t = 0.650, p = 0.5193) (Fig. 4 lower). It has to be emphasized, however, that the strength of this comparison is very limited due to the small number of patients in the endovascularly treated group. In regard to their GOS scores, patients with higher CRP levels in serum (correlation coefficient methodology; z = −5.861, p < 0.0001, r = −0.74) (Fig. 5 upper) and CSF (z = −5.091, p < 0.0001, r = −0.68) (Fig. 5 lower) had less favorable outcomes. A statistically significant inverse correlation was established in our series between CRP levels (in serum and CSF) and GOS scores. A similar statistically strong relationship was found between mRS scores on discharge and CRP measurements in serum (correlation coefficient methodology; z = 6.062, p < 0.0001, r = 0.76) and CSF (z = 5.304, p < 0.0001, r = 0.70).

Fig. 4.
Fig. 4.

Upper: Graph showing CRP measurements in serum in surgically versus endovascularly treated patients in our cohort. Lower: Graph showing CRP measurements in CSF in surgically versus endovascularly treated patients in our study.

Fig. 5.
Fig. 5.

Upper: Schematic representation of CRP measurements in serum in patients with GOS score ≥ 4 versus patients with GOS score < 4 at discharge. Lower: Schematic representation of CRP levels in CSF in patients with GOS score ≥ 4 versus patients with GOS score < 4 at discharge.

Discussion

The role of inflammation in the development and maintenance of cerebral vasospasm has been previously demonstrated.11,55 Several animal studies and clinical series have shown that inflammatory processes contribute to the pathogenesis of cerebral vasospasm.33,54,57 It is well known that leukocyte trafficking increases in SAH due to a breakdown of the blood-brain barrier.5,8–11,14,23,52,66 Increased levels of various soluble adhesion molecules (such as E-selectin, intercellular adhesion molecule-1, and vascular adhesion molecule-1) and cytokines (such as IL-6 and IL-1) have been noted in the plasma and CSF of patients with SAH.11,12,16,22,30,54,57,60 Kubo et al.34 demonstrated that serum concentrations of intercellular adhesion molecule–1 and vascular adhesion molecule–1 were significantly higher among patients suffering aSAH, and that their increased serum levels of these molecules were associated with increased incidence of DIND. An increased concentration of platelet-activating factors was found in the jugular venous blood samples of patients with SAH,22 and tumor necrosis factor–α levels increased after SAH, and this increased concentration was correlated in time and extent with increased blood flow velocities of the basal cerebral arteries as measured by transcranial Doppler ultrasonography.11,12 Furthermore, increased levels of immunoglobulins and complement factors have been found in the serum and cerebral vessel walls during vasospasm.11,24,30,48,50,51 Kubota et al.,35 in an animal model of SAH, found that activated macrophages and T-cell counts were elevated in such circumstances, with peak levels occurring 2 days after the ictal event. In addition, it has been demonstrated that endothelin-1, which is produced by activated leukocytes accompanying an inflammatory response, is involved in the development of cerebral vasospasm.11 Furthermore, recent series of animal models of SAH have shown changes in the gene expression of inflammation-related products.1,11,16,21,31,32,36,38–42,45–47,49,59,62,67 Cyclooxygenase (also called COX-2), which is known to be an important component in many inflammatory responses, is upregulated after induced SAH in canine and rabbit basilar arteries.49,64 Macdonald and Weir,38 in their SAH primate model studies, have demonstrated the upregulation of certain inflammation-related genes.

It is apparent that multiple inflammatory mechanisms are directly involved in the pathogenesis of cerebral vasospasm. It is also well established that CRP is a sensitive inflammatory marker. Interleukin-6 constitutes a strong stimulus for CRP synthesis by hepatocytes.44,63 Additionally, IL-1, which has been implicated in the pathogenesis of cerebral vasospasm, also represents a strong stimulus for CRP synthesis.63 Therefore, elevated concentrations of CRP may well be associated with an increased possibility of developing cerebral vasospasm and subsequently a DIND.34

Our results showed that elevated CRP levels in serum and CSF were associated with increased incidence of angiographic vasospasm, based on the DS angiography findings in our cohort. Additionally, there was a strong inverse correlation between admitting GCS scores and CRP levels in serum and CSF (r = −0.87 and r = −0.78, respectively). The admission Hunt and Hess and Fisher grades were also correlated in a statistically significant fashion with the CRP measurements in serum and CSF in our cohort. Furthermore, the elevated CSF and serum CRP levels that we observed were associated with worse clinical outcome, as expressed in GOS and mRS scores in our cohort. It is noteworthy that the CRP levels were always higher in CSF than in serum in all patients throughout the entire postictal period. This may be explained by the fact that the underlying aSAH caused a disruption of the blood-brain barrier, which allowed massive intrathecal CRP transportation as an immediate systemic inflammatory response to the presence of blood and blood clots in the subarachnoid space. We found no statistically significant difference in the occurrence of angiographic vasospasm between patients undergoing surgical treatment and those undergoing endovascular coil occlusion. Interestingly, the surgically treated group demonstrated higher levels of CRP in serum and CSF compared with those who were endovascularly treated; however, this difference did not reach levels of statistical significance. It has to be emphasized that the extraction of any powerful conclusions from these last comparisons is impossible due to the very limited number of endovascularly treated patients in our study.

Our current findings are in agreement with the observations of other clinical investigators.2,28,34,56,63 Bengzon et al. examined the serum CRP levels of patients undergoing standard neurosurgical procedures in a prospective clinical study. They found that all their patients demonstrated elevated CRP levels postoperatively, and the magnitude of the CRP elevation was associated with the extent of the surgical trauma. They reported, however, that patients with aSAH showed the highest serum CRP increases, and they postulated that the SAH and not the surgical trauma itself had most likely contributed to the significant serum CRP elevation. In a previous retrospective clinical study, by analyzing the patients' admission Hunt and Hess grades, Rothoerl et al.56 found that serum CRP levels could provide independent information regarding the severity of brain injury resulting from the initial SAH. They concluded that the higher the serum CRP level, the poorer the clinical outcome was. Furthermore, the time pattern of serum CRP increase in their cohort was similar to the one observed in our current series. They noted a peak serum CRP concentration on the 3rd and 4th postictal days and gradual, slow decrease of the measurements obtained after the 5th postictal day, a pattern identical to the one observed in our series. Likewise, Takizawa et al.,63 in their study examining CSF samples of patients suffering SAH by using enzyme-linked immunosorbent assays and Western blot analysis, found that CRP levels in CSF were significantly increased, and the CRP in CSF peaked between the 2nd and 3rd postictal days. On the contrary, Berger et al.3 reported that serum CRP reached a peak on the 2nd postictal day in their series. Kacira et al.28 reported increased high-sensitivity CRP levels in serum and CSF in patients with aSAH compared with healthy controls. Interestingly, they found that elevated serum and CSF high-sensitivity CRP was correlated to increased measurements of caspase-3 and neuron-specific enolase, which are markers of apoptosis and neuronal tissue damage, respectively. In a previous study, Fountas et al.13 found that patients with aSAH who had low (< 8) GCS scores and high (> III) Hunt and Hess grades had significantly higher serum CRP levels, and that an increased serum CRP level was positively correlated with poor clinical outcome. Their findings are in agreement with the data in our current study.

Unfortunately, the clinical significance of elevated serum CRP measurements in patients sustaining aSAH is confounded by the fact that most of these patients may have other concomitant systemic infections or pathological conditions that could potentially result in increased CRP serum concentrations. Additionally, the surgical manipulation in these patients (arterial catheterization, surgical clipping, endovascular coil occlusion, ventriculostomy insertion) could influence the systemic CRP levels. However, our strict inclusion criteria minimized the influence of other confounding factors such as systemic infection or other concomitant heart conditions. Moreover, obtaining CRP measurements in CSF could further minimize the effect of other confounding factors in our current study.

It has to be emphasized however, that our study carries significant limitations. First, the size of our clinical series was limited, and therefore the statistical strength of our conclusions was also limited. Second, it is well known that clinical outcome in patients with aSAH is multifactorial. The association between CRP levels systemically and in CSF with the clinical outcome may well be influenced by other parameters in a complex and frequently unpredictable way. In addition, CRP represents a sensitive but nonspecific inflammatory marker. Although we attempted to minimize the presence of other systemic or confounding factors in our study by applying strict inclusion criteria, there were certain issues that could not be addressed. The insidious onset of a CNS and/or systemic infection may contribute to serum CRP elevation and significantly confound the CRP predictive value for early vasospasm detection. Furthermore, any neurosurgical intervention per se may well increase the serum CRP levels,2 although there are no data as far as we know regarding the CRP response in CSF to standard neurosurgical procedures. It has been reported, however, that CRP levels in CSF are elevated in patients with severe head trauma,20,27 a finding that may further support our current results that the postictal elevated CRP levels in CSF are mainly caused by the aSAH insult to the brain parenchyma. A large-scale, multiinstitutional, prospective clinical study is necessary to validate our results and to determine the role of CRP in serum and/or CSF in the identification of patients at high risk for developing cerebral vasospasm.

Conclusions

Our prospective clinical study showed that patients with aSAH who were admitted with low GCS scores and high Hunt and Hess and Fisher grades had elevated CRP levels in serum and CSF. The CRP measurements in the CSF were higher than the serum CRP values in all our patients throughout the entire postictal period. Patients developing angiographic vasospasm demonstrated increased levels of CRP in serum and CSF in our cohort. In addition, the CRP levels in serum and CSF were associated with poor clinical outcome in a statistically significant fashion in our study. Further validation of our results is necessary to define the prognostic role of CRP in identifying patients who are at high risk for developing postictal cerebral vasospasm secondary to aSAH.

Disclaimer

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

References

  • 1

    Aihara YKasuya HOnda HHori TTakeda J: Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage. Stroke 32:2122172001

  • 2

    Bengzon JGrubb ABune AHeillstrom KLindstrom VBrandt L: C-reactive protein levels following standard neurosurgical procedures. Acta Neurochir (Wien) 145:6676712003

  • 3

    Berger MMSoguel LShenkin ARevelly JPPinget CBaines M: Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients. Crit Care 12:R1012008

  • 4

    Berk BCWeintraub WSAlexander RW: Elevation of Creactive protein in “active” coronary artery disease. Am J Cardiol 65:1681721990

  • 5

    Bundy GMMerchant RE: Basic research applied to neurosurgery: lymphocyte trafficking to the central nervous system. Neurosurg Q 6:51681996

  • 6

    Carr WP: The role of the laboratory in rheumatology. Acutephase proteins. Clin Rheum Dis 9:2272391983

  • 7

    Dietrich HHDacey RG Jr: Molecular keys to the problems of cerebral vasospasm. Neurosurgery 46:5175302000

  • 8

    Doczi T: The pathogenetic and prognostic significance of blood–brain barrier damage at the acute stage of aneurysmal subarachnoid hemorrhage. Clinical and experimental studies. Acta Neurochir (Wien) 77:1101321985

  • 9

    Doczi TAmbrose JO'Laoire S: Significance of contrast enhancement after subarachnoid hemorrhage. J Neurosurg 60:3353421984

  • 10

    Doczi TJoo FSonkodi SAdam G: Blood–brain barrier damage during the acute stage of subarachnoid hemorrhage, as exemplified by a new animal model. Neurosurgery 18:7337391986

  • 11

    Dumont ASDumont RJChow MMLin CCalisaneller TLey KF: Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 53:1231352003

  • 12

    Fassbender KHodapp BRossol SBertsch TSchmeck JSchutt S: Inflammatory cytokines in subarachnoid hemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry 70:5345372001

  • 13

    Fountas KNKassam MMachinis TGDimopoulos VGRobinson JS IIIAjjan M: C-reactive protein might predict outcome in aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl (Wien) 104:3773812008

  • 14

    Germano ADavella DCicciarello RHayes RLTomasello F: Blood brain barrier permeability changes after experimental subarachnoid hemorrhage. Neurosurgery 30:8828861992

  • 15

    Haley EJKassell NFTorner JC: The International Cooperative Study on the timing of aneurysm surgery: the North American experience. Stroke 23:2052141992

  • 16

    Handa YKubota TKaneko MTsuchida AKobayashi HKawano H: Expression of intercellular adhesion molecule 1 (ICAM-1) on the cerebral artery following subarachnoid hemorrhage in rats. Acta Neurochir (Wien) 132:92971995

  • 17

    Hansen-Schwartz J: Cerebral vasospasm: a consideration of the various cellular mechanisms involved in the pathophysiology. Neurocrit Care 1:235246712004

  • 18

    Harrod CGBendok BRBatjer HH: Prediction of cerebral vasospasm in patients presenting with aneurysmal subarachnoid hemorrhage: a review. Neurosurgery 56:6336542005

  • 19

    Heilbronn LKClifton PM: C-reactive protein and coronary artery disease: influence of obesity, caloric restriction and weight loss. J Nutr Biochem 13:3163212002

  • 20

    Hergenroeder GRedell JBMoore ANDubinsky WPFunk RTCrommett J: Identification of serum biomarkers in brain-injured adults: potential for predicting elevated intracranial pressure. J Neurotrauma 25:79932008

  • 21

    Hino ATokuyama YKobayashi MYano MWeir BTakeda J: Increased expression of endothelin B receptor mRNA following subarachnoid hemorrhage in monkeys. J Cereb Blood Flow Metab 16:6886971996

  • 22

    Hirashima YNakamura SEndo SKuwayama NNaruse YTakaku A: Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid hemorrhage. Neurochem Res 22:124912551997

  • 23

    Ho HWBatjer HHAneurysmal subarachnoid hemorrhage: pathophysiology and sequelae. Batjer HH: Cerebrovascular Disease Lippincott-Raven PublishersPhiladelphia1997. 889899

  • 24

    Hoshi TShimizu TKito KYamasaki NTakahashi KTakahashi M: Immunological study of late cerebral vasospasm in subarachnoid hemorrhage: detection of immunoglobulins, C3, and fibrinogen in cerebral arterial walls by immunofluorescence method. Neuro Med Chir (Tokyo) 24:6476541984

  • 25

    Hung MJCherng WJCheng CWYang NI: Effect of antispastic agents (calcium antagonists and/or isosorbide dinitrate) on high-sensitivity C-reactive protein in patients with coronary vasospastic angina pectoris and no hemodynamically significant coronary artery disease. Am J Cardiol 95:84872005

  • 26

    Hung MJCherng WJYang NICheng CWLi LF: Relation of high-sensitivity C-reactive protein level with coronary vasospastic angina pectoris in patients without hemodynamically significant coronary artery disease. Am J Cardiol 96:148414902005

  • 27

    Is MCoskun ASanus GZTanriverdi TKafadar AMHanimoglu H: High-sensitivity C-reactive protein levels in cerebrospinal fluid and serum in severe head injury: relationship to tumor necrosis factor-alpha and interleukin-6. J Clin Neurosci 14:116311712007

  • 28

    Kacira TKemerdere RAtukeren PHanimoglu HZihni Sanus GKucur M: Detection of capsace-3, neuron specific enolase, and high-sensitivity C-reactive protein levels in both cerebrospinal fluid and serum of patients after aneurysmal subarachnoid hemorrhage. Neurosurgery 60:6746802007

  • 29

    Kassell NFSasaki TColohan ARTNazar G: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 16:5625721985

  • 30

    Kasuya HShimizu T: Activated complement components C3a and C4a in cerebrospinal fluid and plasma following subarachnoid hemorrhage. J Neurosurg 71:7417461989

  • 31

    Kasuya HWeir BKShen YHariton GVollrath BGhahary A: Procollagen type I and III and transforming growth factorbeta gene expression in the arterial wall after exposure to periarterial blood. Neurosurgery 33:7167221993

  • 32

    Kasuya HWeir BKNakane MPollock JSJohns LMarton LS: Nitric oxide synthase and guanylate cyclase levels in canine basilar artery after subarachnoid hemorrhage. J Neurosurg 82:2502551995

  • 33

    Kaynar MYTanriverdi TKafadar AMKacira TUzun HAydin S: Detection of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both cerebrospinal fluid and serum of patients after aneurysmal subarachnoid hemorrhage. J Neurosurg 101:103010362004

  • 34

    Kubo YOgasawara KKakino SKashimura HTomitsuka NSugawara A: Serum inflammatory adhesion molecules and high-sensitivity C-reactive protein correlates with delayed ischemic neurologic deficits after subarachnoid hemorrhage. Surg Neurol 69:5925962008

  • 35

    Kubota THanda YTsuchida AKaneko MKobayashi HKubota T: The kinetics of lymphocyte subsets and macrophages in subarachnoid space after subarachnoid hemorrhage in rats. Stroke 24:199320011993

  • 36

    Kuroki MKanamaru KSuzuki HWaga SSemba R: Effect of vasospasm on heme oxygenases in a rat model of subarachnoid hemorrhage. Stroke 29:6836891998

  • 37

    Lin CLJeng AYHowng SLKwan AL: Endothelin and subarachnoid hemorrhage-induced cerebral vasospasm: pathogenesis and treatment. Curr Med Chem 11:177917912004

  • 38

    Macdonald RLWeir BMolecular biology and genetics. Macdonald RLWeir B: Cerebral Vasospasm San DiegoAcademic Press2001. 476508

  • 39

    Matz PGMassa SMWeinstein PRTurner CPanter SSSharp FR: Focal hyperexpression of hemeoxygenase-1 protein and messenger RNA in rat brain caused by cellular stress following subarachnoid injections of lysed blood. J Neurosurg 85:8929001996

  • 40

    Matz PGSundaresan SSharp FRWeinstein PR: Induction of HSP70 in rat brain following subarachnoid hemorrhage produced by endovascular perforation. J Neurosurg 85:1381451996

  • 41

    Matz PTurner CWeinstein PRMassa SMPanter SSSharp FR: Heme oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage. Brain Res 713:2112221996

  • 42

    Matz PWeinstein PStates BHonkaniemi JSharp FR: Subarachnoid injections of lysed blood induce hsp70 stress gene and produce DNA fragmentation in focal areas of the rat brain. Stroke 27:5045131996

  • 43

    Mayberg MRBatjer HHDacey RG JrDiringer MHaley ECHeros RC: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 25:231523281994

  • 44

    Mazlam MZHodgson HJ: Interrelations between interleukin-6, interleukin-1 beta, plasma C-reactive protein values, and in vitro C-reactive protein generation in patients with inflammatory bowel disease. Gut 35:77831994

  • 45

    Mima TMostafa MGMori K: Therapeutic dose and timing of administration of RNA synthesis inhibitors for preventing cerebral vasospasm after subarachnoid hemorrhage. Acta Neurochir Suppl (Wien) 70:65671997

  • 46

    Onda HKasuya HTakakura KHori TImaizumi TTakeuchi T: Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage. J Cereb Blood Flow Metab 19:127912881999

  • 47

    Ono SZhang ZDMarton LSYamini BWindmeyer EJohns L: Heme oxygenase-1 and ferritin are increased in cerebral arteries after subarachnoid hemorrhage in monkeys. J Cereb Blood Flow Metab 20:106610762000

  • 48

    Ostergaard JRKristensen BOSvehag SETeisner BMiletic T: Immune complexes and complement activation following rupture of intracranial saccular aneurysms. J Neurosurg 66:8918971987

  • 49

    Osuka KSuzuki YWatanabe YTakayasu MYoshida J: Inducible cyclo-oxygenase expression in canine basilar artery after experimental subarachnoid hemorrhage. Stroke 29:121912221998

  • 50

    Pellettieri LCarlson CALindholm L: Is the vasospasm following subarachnoid hemorrhage an immunoreactive disease?. Experientia 37:117011711981

  • 51

    Pellettieri LNilsson BCarlsson CANilsson U: Serum immunocomplexes in patients with subarachnoid hemorrhage. Neurosurgery 19:7677711986

  • 52

    Peterson EWCardoso ER: The blood-brain barrier following experimental subarachnoid hemorrhage. Part I: Response to insult caused by arterial hypertension. J Neurosurg 58:3383441983

  • 53

    Pluta RM: Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment. Pharmacol Ther 105:23562005

  • 54

    Polin RSBavbek MShaffrey MEBillups KBogaev CAKassell NF: Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage. J Neurosurg 89:5595671998

  • 55

    Provencio JJVora N: Subarachnoid hemorrhage and inflammation; bench to bedside and back. Semin Neurol 25:4354442005

  • 56

    Rothoerl RDAxmann CPina ALWoertgen CBrawanski A: Possible role of C-reactive protein and white blood cell count in the pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 18:68722006

  • 57

    Rothoerl RDSchebesch KMKubitza MWoertgen CBrawanski APina AL: ICAM-1 and VCAM-1 expression following aneurysmal subarachnoid hemorrhage and their possible role in the pathophysiology of subsequent ischemic deficits. Cerebrovasc Dis 22:1431492006

  • 58

    Schievink WI: Intracranial aneurysms. N Engl J Med 336:28401997

  • 59

    Shigeno TMima TYanagisawa MSaito AGoto KYamashita K: Prevention of cerebral vasospasm by actinomycin D. J Neurosurg 74:9409431991

  • 60

    Sills AKClatterbuck REThompson RCCohen PLTamargo RJ: Endothelial expression of intercellular adhesion molecule-1 (ICAM-1) in experimental vasospasm. Neurosurgery 41:4534611997

  • 61

    Soejima HMiyamoto SKojima SHokamaki JTanaka TKawano H: Coronary spastic angina in patients with connective tissue disease. Circ J 68:3673702004

  • 62

    Suzuki HKanamaru KTsunoda HInada HKuroki MSun H: Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats. J Clin Invest 104:59661999

  • 63

    Takizawa TTada TKitazawa KTanaka YHongo KKameko M: Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage. Neurol Res 23:7247302001

  • 64

    Tran Dinh YRJomaa ACallebert JReynier-Rebuffel AMTedgui ASavarit A: Overexpression of cyclooxygenase-2 in rabbit basilar artery endothelial cells after subarachnoid hemorrhage. Neurosurgery 48:6266352001

  • 65

    Umemoto SSuzuki NFujii KFujii AFujii TIwami T: Eosinophil counts and plasma fibrinogen in patients with vasospastic angina pectoris. Am J Cardiol 85:7157192000

  • 66

    von Holst HEricson KEdner G: Positron emission tomography with 68-Ga-EDTA and computed tomography in patients with subarachnoid hemorrhage. Acta Neurochir (Wien) 97:1461491989

  • 67

    Wang XMarton LSWeir BKMacdonald RL: Immediate early gene expression in vascular smooth muscle cells synergistically induced by hemosylate components. J Neurosurg 90:108310901999

If the inline PDF is not rendering correctly, you can download the PDF file here.

Article Information

Address correspondence to: Kostas N. Fountas, M.D., Ph.D., Department of Neurosurgery, Building A, 3rd Floor, Suite #56, University Hospital of Larisa Mezourlo, Larisa 41110, Greece. email: fountas@med.uth.gr.

© AANS, except where prohibited by US copyright law.

Headings

Figures

  • View in gallery

    Schematic representation of summated measured CRP levels in the serum and CSF of our patients.

  • View in gallery

    Upper: Schematic representation of CRP levels in serum in patients with and without vasospasm. Lower: Schematic representation of CRP levels in CSF in patients with and without vasospasm.

  • View in gallery

    Upper: Schematic representation of CRP levels in serum with regard to the admission GCS score. Lower: Schematic representation of CRP levels in CSF with regard to the admission GCS score.

  • View in gallery

    Upper: Graph showing CRP measurements in serum in surgically versus endovascularly treated patients in our cohort. Lower: Graph showing CRP measurements in CSF in surgically versus endovascularly treated patients in our study.

  • View in gallery

    Upper: Schematic representation of CRP measurements in serum in patients with GOS score ≥ 4 versus patients with GOS score < 4 at discharge. Lower: Schematic representation of CRP levels in CSF in patients with GOS score ≥ 4 versus patients with GOS score < 4 at discharge.

References

1

Aihara YKasuya HOnda HHori TTakeda J: Quantitative analysis of gene expressions related to inflammation in canine spastic artery after subarachnoid hemorrhage. Stroke 32:2122172001

2

Bengzon JGrubb ABune AHeillstrom KLindstrom VBrandt L: C-reactive protein levels following standard neurosurgical procedures. Acta Neurochir (Wien) 145:6676712003

3

Berger MMSoguel LShenkin ARevelly JPPinget CBaines M: Influence of early antioxidant supplements on clinical evolution and organ function in critically ill cardiac surgery, major trauma, and subarachnoid hemorrhage patients. Crit Care 12:R1012008

4

Berk BCWeintraub WSAlexander RW: Elevation of Creactive protein in “active” coronary artery disease. Am J Cardiol 65:1681721990

5

Bundy GMMerchant RE: Basic research applied to neurosurgery: lymphocyte trafficking to the central nervous system. Neurosurg Q 6:51681996

6

Carr WP: The role of the laboratory in rheumatology. Acutephase proteins. Clin Rheum Dis 9:2272391983

7

Dietrich HHDacey RG Jr: Molecular keys to the problems of cerebral vasospasm. Neurosurgery 46:5175302000

8

Doczi T: The pathogenetic and prognostic significance of blood–brain barrier damage at the acute stage of aneurysmal subarachnoid hemorrhage. Clinical and experimental studies. Acta Neurochir (Wien) 77:1101321985

9

Doczi TAmbrose JO'Laoire S: Significance of contrast enhancement after subarachnoid hemorrhage. J Neurosurg 60:3353421984

10

Doczi TJoo FSonkodi SAdam G: Blood–brain barrier damage during the acute stage of subarachnoid hemorrhage, as exemplified by a new animal model. Neurosurgery 18:7337391986

11

Dumont ASDumont RJChow MMLin CCalisaneller TLey KF: Cerebral vasospasm after subarachnoid hemorrhage: putative role of inflammation. Neurosurgery 53:1231352003

12

Fassbender KHodapp BRossol SBertsch TSchmeck JSchutt S: Inflammatory cytokines in subarachnoid hemorrhage: association with abnormal blood flow velocities in basal cerebral arteries. J Neurol Neurosurg Psychiatry 70:5345372001

13

Fountas KNKassam MMachinis TGDimopoulos VGRobinson JS IIIAjjan M: C-reactive protein might predict outcome in aneurysmal subarachnoid hemorrhage. Acta Neurochir Suppl (Wien) 104:3773812008

14

Germano ADavella DCicciarello RHayes RLTomasello F: Blood brain barrier permeability changes after experimental subarachnoid hemorrhage. Neurosurgery 30:8828861992

15

Haley EJKassell NFTorner JC: The International Cooperative Study on the timing of aneurysm surgery: the North American experience. Stroke 23:2052141992

16

Handa YKubota TKaneko MTsuchida AKobayashi HKawano H: Expression of intercellular adhesion molecule 1 (ICAM-1) on the cerebral artery following subarachnoid hemorrhage in rats. Acta Neurochir (Wien) 132:92971995

17

Hansen-Schwartz J: Cerebral vasospasm: a consideration of the various cellular mechanisms involved in the pathophysiology. Neurocrit Care 1:235246712004

18

Harrod CGBendok BRBatjer HH: Prediction of cerebral vasospasm in patients presenting with aneurysmal subarachnoid hemorrhage: a review. Neurosurgery 56:6336542005

19

Heilbronn LKClifton PM: C-reactive protein and coronary artery disease: influence of obesity, caloric restriction and weight loss. J Nutr Biochem 13:3163212002

20

Hergenroeder GRedell JBMoore ANDubinsky WPFunk RTCrommett J: Identification of serum biomarkers in brain-injured adults: potential for predicting elevated intracranial pressure. J Neurotrauma 25:79932008

21

Hino ATokuyama YKobayashi MYano MWeir BTakeda J: Increased expression of endothelin B receptor mRNA following subarachnoid hemorrhage in monkeys. J Cereb Blood Flow Metab 16:6886971996

22

Hirashima YNakamura SEndo SKuwayama NNaruse YTakaku A: Elevation of platelet activating factor, inflammatory cytokines, and coagulation factors in the internal jugular vein of patients with subarachnoid hemorrhage. Neurochem Res 22:124912551997

23

Ho HWBatjer HHAneurysmal subarachnoid hemorrhage: pathophysiology and sequelae. Batjer HH: Cerebrovascular Disease Lippincott-Raven PublishersPhiladelphia1997. 889899

24

Hoshi TShimizu TKito KYamasaki NTakahashi KTakahashi M: Immunological study of late cerebral vasospasm in subarachnoid hemorrhage: detection of immunoglobulins, C3, and fibrinogen in cerebral arterial walls by immunofluorescence method. Neuro Med Chir (Tokyo) 24:6476541984

25

Hung MJCherng WJCheng CWYang NI: Effect of antispastic agents (calcium antagonists and/or isosorbide dinitrate) on high-sensitivity C-reactive protein in patients with coronary vasospastic angina pectoris and no hemodynamically significant coronary artery disease. Am J Cardiol 95:84872005

26

Hung MJCherng WJYang NICheng CWLi LF: Relation of high-sensitivity C-reactive protein level with coronary vasospastic angina pectoris in patients without hemodynamically significant coronary artery disease. Am J Cardiol 96:148414902005

27

Is MCoskun ASanus GZTanriverdi TKafadar AMHanimoglu H: High-sensitivity C-reactive protein levels in cerebrospinal fluid and serum in severe head injury: relationship to tumor necrosis factor-alpha and interleukin-6. J Clin Neurosci 14:116311712007

28

Kacira TKemerdere RAtukeren PHanimoglu HZihni Sanus GKucur M: Detection of capsace-3, neuron specific enolase, and high-sensitivity C-reactive protein levels in both cerebrospinal fluid and serum of patients after aneurysmal subarachnoid hemorrhage. Neurosurgery 60:6746802007

29

Kassell NFSasaki TColohan ARTNazar G: Cerebral vasospasm following aneurysmal subarachnoid hemorrhage. Stroke 16:5625721985

30

Kasuya HShimizu T: Activated complement components C3a and C4a in cerebrospinal fluid and plasma following subarachnoid hemorrhage. J Neurosurg 71:7417461989

31

Kasuya HWeir BKShen YHariton GVollrath BGhahary A: Procollagen type I and III and transforming growth factorbeta gene expression in the arterial wall after exposure to periarterial blood. Neurosurgery 33:7167221993

32

Kasuya HWeir BKNakane MPollock JSJohns LMarton LS: Nitric oxide synthase and guanylate cyclase levels in canine basilar artery after subarachnoid hemorrhage. J Neurosurg 82:2502551995

33

Kaynar MYTanriverdi TKafadar AMKacira TUzun HAydin S: Detection of soluble intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in both cerebrospinal fluid and serum of patients after aneurysmal subarachnoid hemorrhage. J Neurosurg 101:103010362004

34

Kubo YOgasawara KKakino SKashimura HTomitsuka NSugawara A: Serum inflammatory adhesion molecules and high-sensitivity C-reactive protein correlates with delayed ischemic neurologic deficits after subarachnoid hemorrhage. Surg Neurol 69:5925962008

35

Kubota THanda YTsuchida AKaneko MKobayashi HKubota T: The kinetics of lymphocyte subsets and macrophages in subarachnoid space after subarachnoid hemorrhage in rats. Stroke 24:199320011993

36

Kuroki MKanamaru KSuzuki HWaga SSemba R: Effect of vasospasm on heme oxygenases in a rat model of subarachnoid hemorrhage. Stroke 29:6836891998

37

Lin CLJeng AYHowng SLKwan AL: Endothelin and subarachnoid hemorrhage-induced cerebral vasospasm: pathogenesis and treatment. Curr Med Chem 11:177917912004

38

Macdonald RLWeir BMolecular biology and genetics. Macdonald RLWeir B: Cerebral Vasospasm San DiegoAcademic Press2001. 476508

39

Matz PGMassa SMWeinstein PRTurner CPanter SSSharp FR: Focal hyperexpression of hemeoxygenase-1 protein and messenger RNA in rat brain caused by cellular stress following subarachnoid injections of lysed blood. J Neurosurg 85:8929001996

40

Matz PGSundaresan SSharp FRWeinstein PR: Induction of HSP70 in rat brain following subarachnoid hemorrhage produced by endovascular perforation. J Neurosurg 85:1381451996

41

Matz PTurner CWeinstein PRMassa SMPanter SSSharp FR: Heme oxygenase-1 induction in glia throughout rat brain following experimental subarachnoid hemorrhage. Brain Res 713:2112221996

42

Matz PWeinstein PStates BHonkaniemi JSharp FR: Subarachnoid injections of lysed blood induce hsp70 stress gene and produce DNA fragmentation in focal areas of the rat brain. Stroke 27:5045131996

43

Mayberg MRBatjer HHDacey RG JrDiringer MHaley ECHeros RC: Guidelines for the management of aneurysmal subarachnoid hemorrhage: a statement for healthcare professionals from a special writing group of the Stroke Council, American Heart Association. Stroke 25:231523281994

44

Mazlam MZHodgson HJ: Interrelations between interleukin-6, interleukin-1 beta, plasma C-reactive protein values, and in vitro C-reactive protein generation in patients with inflammatory bowel disease. Gut 35:77831994

45

Mima TMostafa MGMori K: Therapeutic dose and timing of administration of RNA synthesis inhibitors for preventing cerebral vasospasm after subarachnoid hemorrhage. Acta Neurochir Suppl (Wien) 70:65671997

46

Onda HKasuya HTakakura KHori TImaizumi TTakeuchi T: Identification of genes differentially expressed in canine vasospastic cerebral arteries after subarachnoid hemorrhage. J Cereb Blood Flow Metab 19:127912881999

47

Ono SZhang ZDMarton LSYamini BWindmeyer EJohns L: Heme oxygenase-1 and ferritin are increased in cerebral arteries after subarachnoid hemorrhage in monkeys. J Cereb Blood Flow Metab 20:106610762000

48

Ostergaard JRKristensen BOSvehag SETeisner BMiletic T: Immune complexes and complement activation following rupture of intracranial saccular aneurysms. J Neurosurg 66:8918971987

49

Osuka KSuzuki YWatanabe YTakayasu MYoshida J: Inducible cyclo-oxygenase expression in canine basilar artery after experimental subarachnoid hemorrhage. Stroke 29:121912221998

50

Pellettieri LCarlson CALindholm L: Is the vasospasm following subarachnoid hemorrhage an immunoreactive disease?. Experientia 37:117011711981

51

Pellettieri LNilsson BCarlsson CANilsson U: Serum immunocomplexes in patients with subarachnoid hemorrhage. Neurosurgery 19:7677711986

52

Peterson EWCardoso ER: The blood-brain barrier following experimental subarachnoid hemorrhage. Part I: Response to insult caused by arterial hypertension. J Neurosurg 58:3383441983

53

Pluta RM: Delayed cerebral vasospasm and nitric oxide: review, new hypothesis, and proposed treatment. Pharmacol Ther 105:23562005

54

Polin RSBavbek MShaffrey MEBillups KBogaev CAKassell NF: Detection of soluble E-selectin, ICAM-1, VCAM-1, and L-selectin in the cerebrospinal fluid of patients after subarachnoid hemorrhage. J Neurosurg 89:5595671998

55

Provencio JJVora N: Subarachnoid hemorrhage and inflammation; bench to bedside and back. Semin Neurol 25:4354442005

56

Rothoerl RDAxmann CPina ALWoertgen CBrawanski A: Possible role of C-reactive protein and white blood cell count in the pathogenesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage. J Neurosurg Anesthesiol 18:68722006

57

Rothoerl RDSchebesch KMKubitza MWoertgen CBrawanski APina AL: ICAM-1 and VCAM-1 expression following aneurysmal subarachnoid hemorrhage and their possible role in the pathophysiology of subsequent ischemic deficits. Cerebrovasc Dis 22:1431492006

58

Schievink WI: Intracranial aneurysms. N Engl J Med 336:28401997

59

Shigeno TMima TYanagisawa MSaito AGoto KYamashita K: Prevention of cerebral vasospasm by actinomycin D. J Neurosurg 74:9409431991

60

Sills AKClatterbuck REThompson RCCohen PLTamargo RJ: Endothelial expression of intercellular adhesion molecule-1 (ICAM-1) in experimental vasospasm. Neurosurgery 41:4534611997

61

Soejima HMiyamoto SKojima SHokamaki JTanaka TKawano H: Coronary spastic angina in patients with connective tissue disease. Circ J 68:3673702004

62

Suzuki HKanamaru KTsunoda HInada HKuroki MSun H: Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats. J Clin Invest 104:59661999

63

Takizawa TTada TKitazawa KTanaka YHongo KKameko M: Inflammatory cytokine cascade released by leukocytes in cerebrospinal fluid after subarachnoid hemorrhage. Neurol Res 23:7247302001

64

Tran Dinh YRJomaa ACallebert JReynier-Rebuffel AMTedgui ASavarit A: Overexpression of cyclooxygenase-2 in rabbit basilar artery endothelial cells after subarachnoid hemorrhage. Neurosurgery 48:6266352001

65

Umemoto SSuzuki NFujii KFujii AFujii TIwami T: Eosinophil counts and plasma fibrinogen in patients with vasospastic angina pectoris. Am J Cardiol 85:7157192000

66

von Holst HEricson KEdner G: Positron emission tomography with 68-Ga-EDTA and computed tomography in patients with subarachnoid hemorrhage. Acta Neurochir (Wien) 97:1461491989

67

Wang XMarton LSWeir BKMacdonald RL: Immediate early gene expression in vascular smooth muscle cells synergistically induced by hemosylate components. J Neurosurg 90:108310901999

TrendMD

Metrics

Metrics

All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 201 201 35
PDF Downloads 114 114 18
EPUB Downloads 0 0 0

PubMed

Google Scholar