Published online before print October 7, 2004, doi: 10.1161/01.STR.0000144654.79393.cf
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
(Stroke. 2004;35:2506.)
© 2004 American Heart Association, Inc.
Original Contributions |
Early Vasospasm on Admission Angiography in Patients with Aneurysmal Subarachnoid Hemorrhage Is a Predictor for In-Hospital Complications and Poor Outcome
From the Neurocritical Care and Acute Stroke Program (M.E.B., R.L.N., F.D.G., J.I.F., A.J.R.); the Section of Neurosurgery (R.L.M., J.I.F., A.J.R.), Department of Surgery; and the Department of Neurology (D.H.), Department of Health Studies, the University of Chicago Medical Center and Pritzker School of Medicine, Ill.
Correspondence to Dr Axel J. Rosengart, Assistant Director, Neurocritical Care and Acute Stroke Program, the University of Chicago, 5841 South Maryland Avenue, MC 2030, Chicago, IL 60637. E-mail arosenga{at}neurology.bsd.uchicago.edu
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Background and Purpose— Early vasospasm (EVSP), defined here as arterial narrowing seen on diagnostic angiography within the first 48 hours of aneurysmal rupture, is a rarely reported and poorly defined phenomenon in patients with subarachnoid hemorrhage (SAH). The purpose of this study was to characterize EVSP in a large database of such patients.
Methods— We analyzed the relationship of EVSP to clinical characteristics, in-hospital complications, and outcome at 3 months among 3478 patients entered into 4 prospective, randomized, double-blind, placebo-controlled trials of tirilazad conducted in neurosurgical centers around the world between 1991 and 1997.
Results— Three hundred thirty-nine (10%) of 3478 patients had EVSP. EVSP was significantly more likely in patients with poor neurological grade on admission, history of SAH, intracerebral hematoma, larger aneurysm, thick SAH on cranial computed tomography, and intraventricular hemorrhage. EVSP was not associated with delayed cerebral vasospasm. After adjustment for differences in admission characteristics, EVSP was associated with cerebral infarction (adjusted odds ratios [OR]=1.51; 95% CI, 1.18 to 1.94; P=0.001), neurological worsening (OR=1.41; 95% CI, 1.10 to 1.81; P=0.007), and unfavorable outcome (OR=1.51; 95% CI, 1.15 to 2.00; P=0.003). In addition, there was a trend for patients with increasingly severe EVSP to have unfavorable outcome (OR=1.84 for mild and OR=2.66 for moderate/severe EVSP).
Conclusions— EVSP was seen in 10% of SAH patients and was predictive of cerebral infarction and neurological worsening as well as unfavorable outcome at 3 months. EVSP was not associated with late vasospasm. EVSP may be as important as delayed vasospasm in predicting complications and long-term morbidity in SAH patients.
Key Words: cerebral arteries • cerebral infarction • complications • subarachnoid hemorrhage • vasospasm
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Aneurysmal subarachnoid hemorrhage (SAH) remains a devastating illness with an overall incidence of 6 to 16 per 100 000 population.1,2 Approximately 25% of patients with aneurysmal SAH die within the first 24 hours and
45% do not survive the first month.3 The most important prognostic determinants for outcome are neurological grade on initial examination, volume of subarachnoid blood on initial computerized tomography (CT), age, preexisting hypertension, delayed vasospasm, and rebleeding.4 The commonly discussed form of delayed vasospasm that occurs 4 to 14 days after the SAH and that affects 20% to 30% of patients remains a major cause of morbidity and mortality. In contrast, much less is known about arterial narrowing at the time of or shortly after admission, which has been called early vasospasm (EVSP), ultraearly vasospasm, acute cerebral vasoconstriction, or acute arterial spasm.5,6 This phenomenon is well described in animal models of SAH but its importance in humans remains ill defined.7,8 EVSP was one of many variables collected in the 3500 patients with aneurysmal SAH entered into the 4 randomized international multicenter trials of tirilazad.9–12 The purpose of this study was to identify the prevalence of EVSP and to determine clinical and radiological factors associated with it and its effect on in-hospital complications and outcome of these patients. |
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Patients
We evaluated the data from 3552 patients with aneurysmal SAH that had been recruited into 4 randomized, double-blind, and placebo-controlled trials to evaluate the efficacy of the drug tirilazad.9–12 These trials were conducted in neurosurgical centers in Europe, Australia, New Zealand, the United States, Canada, Mexico, and South Africa between 1991 and 1997. Patients were randomly assigned various doses of tirilazad or placebo, given intravenously every 6 hours from day of entry into the trial until day 10 post-SAH. Individuals had to be at least 18 years of age and to begin drug treatment within 48 hours of admission. All grades of SAH were eligible and all patients had angiographically documented saccular aneurysms with SAH confirmed by CT or lumbar puncture. Exclusion criteria included (1) nonsaccular aneurysm, (2) severe concomitant illness, (3) serious cardiovascular complications, (4) pregnancy, lactating, and/or (5) taking steroids or calcium channel antagonists other than nimodipine before randomization. Exclusion also occurred if a patient had placement of a detachable coil in the ruptured aneurysm. All patients were administered nimodipine, either orally (60 mg every 4 hours) or intravenously (2 mg/h) for 14 days after admission.9–12
Definition of Clinical and Radiological Variables
Neurological grade was classified by the World Federation of Neurological Surgeons scale.13 Vital signs were recorded on admission and on day 8 post-SAH. Preexisting medical conditions were documented. Prophylactic and therapeutic hemodynamic (hemodilution, induced hypertension, and hypervolemia) therapy for symptomatic vasospasm after day 2 was recorded. Data on in-hospital complications included neurological worsening, cerebral infarction and edema, hydrocephalus and pulmonary edema.
Symptomatic vasospasm was defined by clinical criteria and included (1) symptoms between days 5 and 12 after SAH: worsening headache, stiff neck or low grade fever; insidious onset of confusion or decline in level of consciousness; and focal deficit; (2) a head CT scan excluding other causes of worsening; and (3) no other identifiable cause of neurological worsening. Neurological worsening was defined as a 
2 point decrease in the modified Glasgow coma score or a 2 point increase in the motor score of the National Institutes of Health Stroke Scale lasting for 8 hours.14 Outcome was graded 3 months post-SAH using the Glasgow outcome scale (GOS).15
Radiographic data included grading of the amount of subarachnoid blood on the initial CT scan as none, diffuse or localized thin, or diffuse or localized thick, as well as presence of intraventricular or intracerebral hemorrhage, and hydrocephalus. Selected anteroposterior and lateral angiography films were forwarded to a central registry for blinded evaluation. Luminal narrowing of the intracranial arteries not the result of intrinsic disease, such as arteriosclerosis, identified on initial angiography performed within 48 hours of SAH was defined as EVSP and recorded as present or absent. Two of the trials also recorded the degree of luminal narrowing as either mild (minimal narrowing), moderate (25% to 50% narrowing), or severe (>50% arterial narrowing). An image analysis system was used to obtain the measurements of arterial lumen diameters. Location and size of the ruptured aneurysm was classified as previously described.9–12
Statistical Analysis
Univariate analysis was performed first to detect significant differences in demographic and clinical characteristics, radiographic findings, and treatments between patients with and without EVSP. Two sample t tests or Wilcoxon rank sum tests were used for continuous variables and 
2 tests were used for categorical variables. Also, 2 test was used to examine whether the prevalence of EVSP was homogenous across 4 clinical trials. Next, in-hospital complications and 3-month outcome were analyzed using 2 tests with the relative difference expressed as odds ratios (OR, with 95% CI). The OR was derived from a logistic regression (with outcome dichotomized as favorable [GOS 1 and 2] or unfavorable [GOS 3 to 5]) or proportional odds model (for 5-point GOS at 3 months). Multivariate logistic regression was then used to adjust for the trial indicator variable, dose of tirilazad, and for variables identified to be significantly different between patients with and without EVSP. To examine the homogeneity of effect across trials, we tested the EVSP by trial interaction in the framework of multivariate logistic regression. We also tested the interaction of EVSP with age. The subset of patients with grading of the severity of EVSP was used to identify a possible relationship between severity of EVSP, in-hospital complications, and outcome. To attain statistical stability, moderate and severe EVSP were combined for this analysis. A P value <0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Of 3552 patients enrolled in the trials, 3478 (98%) had data on EVSP and of those, 339 (9.8%) patients had EVSP. Patient demographics were similar between patients with and without EVSP (Table 1). The only significant differences in admission characteristics and past medical illnesses were that patients with poor admission World Federation of Neurological Surgeons grade, history of hypertension, and history of SAH were more likely to have EVSP. The prevalence of EVSP was significantly different between the 4 trials (P=0.035).
|
Patients with EVSP were much more likely to have an intracerebral hematoma or a larger aneurysm (all P<0.0001, Table 2). The proportions of thick subarachnoid blood clots and intraventricular hemorrhage were slightly but significantly higher in patients with EVSP (all P<0.05). Use of anticonvulsant medication, time interval from SAH to surgery, and dose of the study drug tirilazad were not different between groups. However, fewer patients in the EVSP group underwent aneurysm clipping (P<0.0001), and fewer were treated prophylactically with hemodynamic therapy (P=0.01). This likely represents a selection bias, as EVSP patients were generally sicker on admission and hence may have been considered poorer surgical candidates.
|
Three-month outcome, classified either on the expanded 5-point GOS or as a dichotomous variable, was significantly worse in patients with EVSP (P<0.0001, Table 3). In addition, patients with EVSP had significantly higher incidences of neurological worsening, cerebral infarction, and hydrocephalus. No significant difference was found between groups in the incidence of symptomatic delayed vasospasm; use of hypervolemic, hemodilution, or induced hypertension therapy; or use of cerebral angioplasty, cerebral edema, or pulmonary edema.
|
After further adjusting for neurological grade on admission, EVSP was still significantly associated with 3-month GOS on either the 5-point or dichotomous scale. EVSP was also significantly associated with neurological worsening and cerebral infarction but not with hydrocephalus (Table 4). Adjustments for history of hypertension or SAH, thickness of SAH on admission CT scan, intraventricular hemorrhage, intracerebral hemorrhage, aneurysm size, surgical clipping, study drug dosage, and trial indicator did not affect the findings. Patients with EVSP had increased odds of unfavorable GOS (on 5-point scale: OR 1.54; 95% CI, 1.22 to 1.94; on 2-point scale: OR 1.51; 95% CI, 1.15 to 2.00), neurological worsening (OR 1.41; 95% CI, 1.10 to 1.81), and cerebral infarction (OR 1.51; 95% CI, 1.18 to 1.94). In addition, there were no significant differential effects of EVSP on 3-month GOS, neurological worsening, and cerebral infarction across the 4 clinical trials (all P for interaction >0.28). There also was no significant interaction between EVSP and age (all P for interaction >0.66).
|
Subgroup analysis was performed on 1874 patients who had grading of EVSP (no EVSP, n=1691; mild, n=137; and moderate/severe, n=46). After adjustment for neurological grade, a significant trend was noted for GOS outcome and cerebral infarction (Figure). There were, however, no pairwise differences in outcome, neurological worsening, or cerebral infarction between patients with mild and those with moderate or severe EVSP. This might be a result of the small sample size within this category.
|
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
Prospectively collected data on patients with aneurysmal SAH from neurosurgical centers around the world documented EVSP in 339 of 3478 (9.8%) patients. A previous report, restricted to a subgroup of 296 North American patients in this database reported a similar prevalence of EVSP (13%).5 Previous data on EVSP is limited to small case series, most of which are patients diagnosed with EVSP occurring within minutes of aneurysm rerupture during catheter angiography.6,19–21 EVSP also has been diagnosed in association with various other disorders such as rupture of arteriovenous malformations and eclampsia.22–24 Our study found that EVSP was more common in patients with a history of hypertension, previous SAH, poor neurological grade, larger aneurysm size, intracerebral hemorrhage, intraventricular hemorrhage, and thicker subarachnoid clot. Importantly, EVSP was significantly associated with neurological worsening, cerebral infarction, and unfavorable outcome at 3 months. In addition, in-hospital complications of neurological worsening and cerebral infarction tended to be more likely, as the severity of EVSP increased.
Factors associated with delayed vasospasm among patients in this same database were aged 40 to 59, history of hypertension, worse neurological grade, thicker clot on admission CT, larger aneurysm size, intraventricular hemorrhage, prophylactic use of induced hypertension, and not being in the first European tirilazad study.17,18 In our study, EVSP was associated with some of these factors including history of hypertension, worse neurological grade, larger aneurysm size, thicker subarachnoid clot, and intraventricular hemorrhage.
There was no association between EVSP and delayed vasospasm in our analysis, suggesting that the etiology of the 2 phenomena is different. Acute vasoconstriction is well described after experimental SAH,7,8 and several hypotheses have been postulated to explain this phenomenon. Release of vasoconstricting substances from the subarachnoid clot or the arterial wall acutely after SAH may contribute.25–29 In addition, experimental studies suggest that EVSP may be accompanied by microcirculatory abnormalities.30–32 The acute vasospasm documented in animal studies occurs often within minutes to hours of subarachnoid blood release. In humans, acute vasoconstriction has been described with aneurysm rupture occurring at the time of angiography.6 Angiographic narrowing seen with vasospasm may also be secondary because of increased intracranial pressure, stretching of arteries around intracerebral hematomas, subarachnoid clots, or aneurysms themselves or because of preexisting atherosclerosis, arterial hypoplasia, or angiographic artifacts. This raises the possibility that the observed arterial narrowing in some of our patients may be because of one of these factors and explain the associations of EVSP with worse neurological grade, thicker SAH on CT, larger aneurysm size, and intracerebral hemorrhage. Furthermore, the observed association with prior SAH raises the possibility that EVSP actually represents in these patients delayed vasospasm from a prior undiagnosed SAH or an even more remote SAH after which the arteries did not return to normal diameter.
Analysis of all patients in the database regardless of treatment with tirilazad was justified on the basis that the inclusion and exclusion criteria were similar, that EVSP was diagnosed within 48 hours of SAH, that drug or placebo administration was started within 48 hours, and that there are no acute vascular effects of tirilazad.16 Also, in multivariate analysis, we adjusted for tirilazad treatment, eliminating this source of potential confounding. There are some advantages of data pooling of 4 trials including that statistical power is sufficient to detect moderate effect and that bias in outcome measurement from a single study center is unlikely to affect the result. However, the disadvantages, including heterogeneity of population and heterogeneity of effect across trials, should not be ignored. We included trial indicator variable in the multivariate logistic regression to control for potential confounding. We also examined EVSP by trial interactions and found the effects of EVSP on the 3-month outcome, neurological deterioration, and cerebral infarction were homogeneous across the 4 clinical trials.
In summary, EVSP occurs in up to 10% of patients with aneurysmal SAH. EVSP was a significant predictor of neurological deterioration and cerebral infarction during the hospital course and of unfavorable outcome at 3 months. Increased attention to EVSP and its relation to neurological deterioration and recovery may be warranted to better assess SAH patients and to stimulate research on the etiology and pathogenesis.
Received July 9, 2004; accepted August 20, 2004.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Hamada J, Morioka M, Yano S, Kai Y, Ushio Y. Incidence and early prognosis of aneurysmal subarachnoid hemorrhage in Kumamoto Prefecture, Japan. Neurosurgery. 2004; 54: 31–37.[CrossRef][Medline] [Order article via Infotrieve]
2. Ingall TJ, Whisnant JP. Epidemiology of subarachnoid hemorrhage. In: Yanagihara T, Piepgras DG, Atkinson JLD, eds. subarachnoid hemorrhage. Medical and Surgical Management. New York, NY: Marcel Dekker; 1998.
3. Broderick JP, Brott TG, Duldner JE, Tomsick T, Leach A. Initial and recurrent bleeding are the major causes of death following subarachnoid hemorrhage. Stroke. 1994; 25: 1342–1347.[Abstract]
4. Kassell NF, Torner JC, Haley EC Jr, Jane JA, Adams HP, Kongable GL. The International Cooperative Study on the Timing of Aneurysm Surgery. Part 1: overall management results. J Neurosurg. 1990; 73: 18–36.[Medline] [Order article via Infotrieve]
5. Qureshi AI, Sung GY, Suri MA, Straw RN, Guterman LR, Hopkins LN. Prognostic value and determinants of ultraearly angiographic vasospasm after aneurysmal subarachnoid hemorrhage. Neurosurgery. 1999; 44: 967–973.[CrossRef][Medline] [Order article via Infotrieve]
6. Wilkins RH. Aneurysm rupture during angiography: does acute vasospasm occur? Surg Neurol. 1976; 5: 299–303.[Medline] [Order article via Infotrieve]
7. Brawley BW, Strandness DEJ, Kelly WA. The biphasic response of cerebral vasospasm in experimental subarachnoid hemorrhage. J Neurosurg. 1968; 28: 1–8.[Medline] [Order article via Infotrieve]
8. Bederson JB, Levy AL, Ding WH, Kahn R, DiPerna CA, Jenkins AL III, Vallabhajosyula P. Acute vasoconstriction after subarachnoid hemorrhage. Neurosurgery. 1998; 42: 352–360.[Medline] [Order article via Infotrieve]
9. Kassell NF, Haley EC Jr, Apperson-Hansen C, Alves WM. Randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in Europe, Australia, and New Zealand. J Neurosurg. 1996; 84: 221–228.[Medline] [Order article via Infotrieve]
10. Haley EC Jr, Kassell NF, Apperson-Hansen C, Maile MH, Alves WM. A randomized, double-blind, vehicle-controlled trial of tirilazad mesylate in patients with aneurysmal subarachnoid hemorrhage: a cooperative study in North America. J Neurosurg. 1997; 86: 467–474.[Medline] [Order article via Infotrieve]
11. Lanzino G, Kassell NF. Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part II. A cooperative study in North America. J Neurosurg. 1999; 90: 1018–1024.[Medline] [Order article via Infotrieve]
12. Lanzino G, Kassell NF, Dorsch NW, Pasqualin A, Brandt L, Schmiedek P, Truskowski LL, Alves WM. Double-blind, randomized, vehicle-controlled study of high-dose tirilazad mesylate in women with aneurysmal subarachnoid hemorrhage. Part I. A cooperative study in Europe, Australia, New Zealand, and South Africa. J Neurosurg. 1999; 90: 1011–1017.[Medline] [Order article via Infotrieve]
13. Drake CG, Hunt WE, Sano K, Kassell N, Teasdale G, Pertuiset B, DeVilliers JC. Report of World Federation of Neurological Surgeons Committee on a universal subarachnoid hemorrhage grading scale. J Neurosurg. 1988; 68: 985–986.[Medline] [Order article via Infotrieve]
14. Haley EC, Jr., Kassell NF, Torner JC. A randomized controlled trial of high-dose intravenous nicardipine in aneurysmal subarachnoid hemorrhage. A report of the Cooperative Aneurysm Study. J Neurosurg. 1993; 78: 537–547.[Medline] [Order article via Infotrieve]
15. Jennett B, Bond M. Assessment of outcome after severe brain damage. A practical scale. Lancet. 1975; 1: 480–484.[Medline] [Order article via Infotrieve]
16. Hall ED. Efficacy and mechanisms of action of the cytoprotective lipid peroxidation inhibitor tirilazad mesylate in subarachnoid haemorrhage. Eur J Anaesthesiol. 1996; 13: 279–289.[CrossRef][Medline] [Order article via Infotrieve]
17. Dorsch NWC, King MT. A review of cerebral vasospasm in aneurysmal subarachnoid hemorrhage. Part 1: incidence and effects. J Clin Neurosci. 1994; 1: 19–26.[Medline] [Order article via Infotrieve]
18. Macdonald RL, Rosengart A, Huo D, Karrison T. Factors associated with the development of vasospasm after planned surgical treatment of aneurysmal subarachnoid hemorrhage. J Neurosurg. 2003; 99: 644–652.[Medline] [Order article via Infotrieve]
19. Koenig GH, Marshall WH Jr, Poole GJ, Kramer RA. Rupture of intracranial aneurysms during cerebral angiography: report of ten cases and review of the literautre. Neurosurgery. 1979; 5: 314–324.[Medline] [Order article via Infotrieve]
20. Dublin AB, French BN. Cerebral aneurysmal rupture during angiography with confirmation by computed tomography: a review of intra-angiographic aneurysmal rupture. Surg Neurol. 1980; 13: 19–26.[Medline] [Order article via Infotrieve]
21. Taneda M, Otsuki H, Kumura E, Sakaguchi T. Angiographic demonstration of acute phase of intracranial arterial spasm following aneurysm rupture. Case report. J Neurosurg. 1990; 73: 958–961.[CrossRef][Medline] [Order article via Infotrieve]
22. Kothbauer K, Schroth G, Seiler RW, Do DD. Severe symptomatic vasospasm after rupture of an arteriovenous malformation. Am J Neuroradiol. 1995; 16: 1073–1075.[Abstract]
23. Akins PT, Levy KJ, Cross AH, Goldberg MP, Schieber MH. Postpartum cerebral vasospasm treated with hypervolemic therapy. Am J Obstet Gynecol. 1996; 175: 1386–1388.[CrossRef][Medline] [Order article via Infotrieve]
24. Ringer AJ, Qureshi AI, Kim SH, Fessler RD, Guterman LR, Hopkins LN. Angioplasty for cerebral vasospasm from eclampsia. Surg Neurol. 2001; 56: 373–378.[CrossRef][Medline] [Order article via Infotrieve]
25. Maiuri F, Gallicchio B, Donati P, Carandente M. The blood leukocyte count and its prognostic significance in subarachnoid hemorrhage. J Neurosurg Sci. 1987; 31: 45–48.[Medline] [Order article via Infotrieve]
26. Mathiesen T, Edner G, Ulfarsson E, Andersson B. Cerebrospinal fluid interleukin-1 receptor antagonist and tumor necrosis factor-alpha following subarachnoid hemorrhage. J Neurosurg. 1997; 87: 215–220.[Medline] [Order article via Infotrieve]
27. Spallone A, Acqui M, Pastore FS, Guidetti B. Relationship between leukocytosis and ischemic complications following aneurysmal subarachnoid hemorrhage. Surg Neurol. 1987; 27: 253–258.[CrossRef][Medline] [Order article via Infotrieve]
28. Delgado TJ, Arbab MA, Warberg J, Svendgaard NA. The role of vasopressin in acute cerebral vasospasm. Effect on spasm of a vasopressin antagonist or vasopressin antiserum. J Neurosurg. 1988; 68: 266–273.[Medline] [Order article via Infotrieve]
29. Sehba FA, Schwartz AY, Chereshnev I, Bederson JB. Acute decrease in cerebral nitric oxide levels after subarachnoid hemorrhage. J Cereb Blood Flow Metab. 2000; 20: 604–611.[Medline] [Order article via Infotrieve]
30. Jakubowski J, Bell BA, Symon L, Zawirski M, Francis DM. A primate model of subarachnoid hemorrhage: change in regional cerebral blood flow, autoregulation carbon dioxide reactivity, and central conduction time. Stroke. 1982; 13: 601.
31. Ohkuma H, Manabe H, Tanaka M, Suzuki S. Impact of cerebral microcirculatory changes on cerebral blood flow during cerebral vasospasm after aneurysmal subarachnoid hemorrhage. Stroke. 2000; 31: 1621–1627.
32. Ohkuma H, Ogane K, Tanaka M, Suzuki S. Assessment of cerebral microcirculatory changes during cerebral vasospasm by analyzing cerebral circulation time on DSA images. Acta Neurochir Suppl. 2001; 77: 127–130.
This article has been cited by other articles:
 |
|
 |
|
  A.M. Laslo, J.D. Eastwood, P. Pakkiri, F. Chen, and T.Y. Lee CT Perfusion-Derived Mean Transit Time Predicts Early Mortality and Delayed Vasospasm after Experimental Subarachnoid Hemorrhage AJNR Am. J. Neuroradiol., January 1, 2008; 29(1): 79 - 85. [Abstract] [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||