R. Loch Macdonald

Prediction of symptomatic vasospasm after subarachnoid hemorrhage: the modified fisher scale.

OBJECTIVEnWe developed a modification of the Fisher computed tomographic rating scale and compared it with the original Fisher scale to determine which scale best predicts symptomatic vasospasm after subarachnoid hemorrhage.nnnMETHODSnWe analyzed data from 1355 subarachnoid hemorrhage patients in the placebo arm of four randomized, double-blind, placebo-controlled studies of tirilazad. Modified Fisher computed tomographic grades were calculated on the basis of the presence of cisternal blood and intraventricular hemorrhage. Crude odds ratios (OR) reflecting the risk of developing symptomatic vasospasm were calculated for each scale level, and adjusted ORs expressing the incremental risk were calculated after controlling for known predictors of vasospasm.nnnRESULTSnOf 1355 patients, 451 (33%) developed symptomatic vasospasm. For the modified Fisher scale, compared with Grade 0 to 1 patients, the crude OR for vasospasm was 1.6 (95% confidence interval [CI], 1.0-2.5) for Grade 2, 1.6 (95% CI, 1.1-2.2) for Grade 3, and 2.2 (95% CI, 1.6-3.1) for Grade 4. For the original Fisher scale, referenced to Grade 1, the OR for vasospasm was 1.3 (95% CI, 0.7-2.2) for Grade 2, 2.2 (95% CI, 1.4-3.5) for Grade 3, and 1.7 (95% CI, 1.0-3.0) for Grade 4. Early angiographic vasospasm, history of hypertension, neurological grade, and elevated admission mean arterial pressure were identified as risk factors for symptomatic vasospasm. After adjusting for these variables, the modified Fisher scale remained a significant predictor of vasospasm (adjusted OR, 1.28; 95% CI, 1.06-1.54), whereas the original Fisher scale was not.nnnCONCLUSIONnThe modified Fisher scale, which accounts for thick cisternal and ventricular blood, predicts symptomatic vasospasm after subarachnoid hemorrhage more accurately than original Fisher scale.

Predictors of cerebral infarction in patients with aneurysmal subarachnoid hemorrhage.

OBJECTIVECerebral infarction would be expected to be associated with poor outcome after aneurysmal subarachnoid hemorrhage (SAH), although there are few data on which to base this assumption. The goals of this study were to determine the impact of cerebral infarction on outcome and to examine predictors of infarction in these patients. METHODSUnivariate and multivariable statistical methods were used to examine the impact of cerebral infarction on the Glasgow Outcome Scale score 3 months after SAH among 3567 patients entered into four prospective, randomized, double-blind, placebo-controlled trials of tirilazad conducted in neurosurgical centers around the world between 1991 and 1997. Patient demographics, clinical variables, radiographic characteristics, and treatment variables associated with cerebral infarction were also determined by the same methods. RESULTSSeven hundred and seven (26%) out of 2741 patients with complete data had cerebral infarction on computed tomographic scans 6 weeks after SAH. Multivariable logistic regression showed that cerebral infarction increased the odds of unfavorable outcome by a factor of 5.4 (adjusted odds ratio, 5.4; 95% confidence interval, 4.2–6.8; P < 0.0001), which was a higher odds ratio than all other factors associated with outcome. The proportion of explained variance in outcome was also highest for cerebral infarction and accounted for 39% of the explained variance. Multivariable analysis found that cerebral infarction was significantly associated with increasing patient age, worse neurological grade on admission, history of hypertension or diabetes mellitus, larger aneurysm, use of prophylactically or therapeutically induced hypertension, temperature more than 38°C 8 days after SAH, and symptomatic vasospasm. CONCLUSIONCerebral infarction was strongly associated with poor outcome after aneurysmal SAH. The most important potentially treatable factor associated with infarction was symptomatic vasospasm.

Subarachnoid Hemorrhage Grading Scales A Systematic Review

Numerous systems are reported for grading the clinical condition of patients following subarachnoid hemorrhage (SAH). The literature was reviewed for articles pertaining to the grading of such patients, including publications on the Hunt and Hess Scale, Fisher Scale, Glasgow Coma Score (GCS), and World Federation of Neurological Surgeons Scale. This article reviews the advantages and limitations of these scales as well as more recent proposals for other grading systems based on these scales with or without addition of other factors known to be prognostic for outcome after SAH. There remain substantial deficits in the literature regarding grading of patients with SAH. Most grading scales were derived retrospectively, and the intra- and interobserver variability has seldom been assessed. Inclusion of additional factors increases the complexity of the scale, possibly making it less likely to be adopted for routine usage and increasing (only marginally in some cases) the ability to predict prognosis. Until further data are available, it is recommended that publications on patients with SAH report at least the admission GCS as well as factors commonly known to influence prognosis, such as age, pre-existing hypertension, the amount of blood present on admission computed tomography, time of admission after SAH, aneurysm location and size, presence of intracerebral or intraventricular hemorrhage, and blood pressure at admission.

Outcome in patients with subarachnoid hemorrhage treated with antiepileptic drugs.

OBJECTnProphylactic use of antiepileptic drugs (AEDs) in patients admitted with aneurysmal subarachnoid hemorrhage (SAH) is common practice; however, the impact of this treatment strategy on in-hospital complications and outcome has not been systematically studied. The goal in this study was twofold: first, to describe the prescribing pattern for AEDs in an international study population; and second, to delineate the impact of AEDs on in-hospital complications and outcome in patients with SAH.nnnMETHODSnThe authors examined data collected in 3552 patients with SAH who were entered into four prospective, randomized, double-blind, placebo-controlled trials conducted in 162 neurosurgical centers and 21 countries between 1991 and 1997. The prevalence of AED use was assessed by study country and center. The impact of AEDs on in-hospital complications and outcome was evaluated using conditional logistic regressions comparing treated and untreated patients within the same study center.nnnRESULTSnAntiepileptic drugs were used in 65.1% of patients and the prescribing pattern was mainly dependent on the treating physicians: the prevalence of AED use varied dramatically across study country and center (intraclass correlation coefficients 0.22 and 0.66, respectively [p < 0.001]). Other predictors included younger age, worse neurological grade, and lower systolic blood pressure on admission. After adjustment, patients treated with AEDs had odds ratios of 1.56 (95% confidence interval [CI] 1.16-2.10; p = 0.003) for worse outcome based on the Glasgow Outcome Scale; 1.87 (95% CI 1.43-2.44; p < 0.001) for cerebral vasospasm; 1.61 (95% CI 1.25-2.06; p < 0.001) for neurological deterioration; 1.33 (95% CI 1.01-1.74; p = 0.04) for cerebral infarction; and 1.36 (95% CI 1.03-1.80; p = 0.03) for elevated temperature during hospitalization.nnnCONCLUSIONSnProphylactic AED treatment in patients with aneurysmal SAH is common, follows an arbitrary prescribing pattern, and is associated with increased in-hospital complications and worse outcome.

Etiology of Cerebral Vasospasm

Cerebral vasospasm is a gradual onset and prolonged constriction of the cerebral arteries in the subarachnoid space after subarachnoid hemorrhage. The principal cause is the surrounding blood clot. The significance of vasospasm is that flow through the constricted arteries may be reduced sufficiently to cause cerebral infarction. Subarachnoid blood clot is sufficient to cause vasospasm; it does not require additional arterial injury, intracranial hypertension or brain infarction, although these elements are often coexistent. The blood released at the time of aneurysmal rupture into the alien subarachnoid environment is an extraordinarily complex mix of cellular and extracellular elements that evolves as clotting occurs; cells disintegrate; local inflammation, phagocytosis and repair take place; severe constriction alters the metabolism and structure of the arterial wall as well as the balance of vasoconstrictor and dilator substances produced by its endothelium, neurogenic network and perhaps smooth muscle cells.

Cerebral vasospasm and free radicals

The literature implicating free radical reactions in the genesis of cerebral vasospasm following aneurysmal subarachnoid hemorrhage is reviewed. While this condition has features of a prototypical free radical-mediated disease and a plausible theory can be outlined, data to support the theory are limited. An association of lipid peroxidation with vasospasm has been observed, but more sophisticated techniques for detection of free radicals and for detection of free radical damage to arterial wall proteins and nucleic acids have not been used. There are conflicting reports about efficacy of various antioxidant treatments for vasospasm. In these studies, concomitant experiments have usually not confirmed that the treatments have decreased free radicals or lipid peroxides in cerebrospinal fluid. Because smooth muscle contraction is involved in vasospasm, it would be interesting to investigate the actions of free radicals on smooth muscle cells using, for example, isometric tension recordings and patch clamp techniques. Studies of cardiac myocytes indicate that free radicals alter conductances through potassium and calcium channels and through the sodium-calcium exchanger and may result in elevations in intracellular calcium. Few studies have been performed on cerebral smooth muscle cells. In one study, exposure of cerebrovascular smooth muscle cells to free radicals resulted in increased outward currents, decreased membrane resistance, cell contraction, appearance of membrane blebs, and cell death. In summary, more investigations using better experimental techniques are required before free radicals and reactions induced by them can be said with certainty to be the primary cause of vasospasm.

Pathology and Pathogenesis

This chapter focuses on the cerebral infarction from vasospasm. Infarction involves the death of both neurons and glia. Neuronal necrosis follows cell swelling, mitochondrial damage and dissolution and generalized disruption of internal homeostasis. Membranes lyse and intracellular constituents are released extracellularly which can invoke a local inflammatory reaction. This is characterized by cellular infiltration, edema, and vascular damage. Ischemically induced extreme energy failure in mitochondria is the presumed essential cause of necrosis. Focal cerebral ischemia produces infarction characterized by microvacuolation, ischemic cell change with incrustation, and homogenizing cell change. Ischemia may result not just in neuronal death through these rapid mechanisms. A series of molecular and cellular processes underlie the transition from ischemia to inflammation and ultimate tissue dissolution. These involve polymorphonuclear leukocyte activation and chemotaxis, endothelial cell receptor biology, cytokine synthesis and release, leukocyte transmigration, and tissue invasion and microvascular thrombosis. Ischemia from VSP can be aggravated by coexistent vascular occlusive disease and other factors, such as advanced age, hypertension, diabetes mellitus, smoking, coronary artery disease, and elevated lipids. The infarction is related to the total amount, but it is not the distribution or clearance rate of extravasated blood, which is probably not shared by the majority of investigators.

Management of cerebral vasospasm

Cerebral vasospasm is delayed narrowing of the large arteries of the circle of Willis occurring 4 to 14 days after aneurysmal subarachnoid hemorrhage (SAH). It is but one cause of delayed deterioration after SAH but, in general, is the most important potentially treatable cause of morbidity and mortality after SAH. Development of vasospasm is best predicted by the volume, location, persistence and density of subarachnoid clot early after SAH. Diagnosis is made by catheter angiography or, with less accuracy, by computed tomographic angiography, transcranial Doppler ultrasound or other methods. Treatment remains problematic because it is expensive, time-consuming, associated with substantial risk and largely ineffective. Treatment includes optimization of factors that affect cerebral blood flow and metabolism, systemic administration of nimodipine, hemodynamic therapy and pharmacologic and mechanical angioplasty.Cerebral vasospasm is delayed narrowing of the large arteries of the circle of Willis occurring 4 to 14 days after aneurysmal subarachnoid hemorrhage (SAH). It is but one cause of delayed deterioration after SAH but, in general, is the most important potentially treatable cause of morbidity and mortality after SAH. Development of vasospasm is best predicted by the volume, location, persistence and density of subarachnoid clot early after SAH. Diagnosis is made by catheter angiography or, with less accuracy, by computed tomographic angiography, transcranial Doppler ultrasound or other methods. Treatment remains problematic because it is expensive, time-consuming, associated with substantial risk and largely ineffective. Treatment includes optimization of factors that affect cerebral blood flow and metabolism, systemic administration of nimodipine, hemodynamic therapy and pharmacologic and mechanical angioplasty.

Grading of Subarachnoid Hemorrhage: Modification of the World Federation of Neurosurgical Societies Scale on the Basis of Data for a Large Series of Patients

OBJECTIVEThe goals of this study were to use a large, prospectively collected, multicenter database for patients with aneurysmal subarachnoid hemorrhage (SAH) who were treated between 1991 and 1997 to determine the prognostic significance of clinical and radiological factors for outcomes and to use those factors to develop a grading scale to predict outcomes. METHODSA total of 3567 patients with SAH who were entered into four randomized clinical trials of tirilazad were studied. Outcomes were assessed 3 months after SAH, with the Glasgow Outcome Scale. Twenty clinical and radiological factors were entered into univariate and multivariate analyses, to determine factors prognostic for outcomes. Grading scales based on the most powerful prognostic parameters were statistically derived and validated and were compared with the World Federation of Neurosurgical Societies (WFNS) grading scale. RESULTSFactors predictive of outcomes included age, WFNS grade, history of hypertension, systolic blood pressure at admission, ruptured aneurysm location and size, blood clot thickness on computed tomographic scans, and angiographic vasospasm at admission. A grading scale using these factors could be derived; it predicted outcomes more accurately than did the WFNS scale, although it would be more complex to use. CONCLUSIONOutcome prediction after SAH can be improved by adding additional clinical and radiological factors to the WFNS scale, albeit with added complexity.

Early Vasospasm on Admission Angiography in Patients with Aneurysmal Subarachnoid Hemorrhage Is a Predictor for In-Hospital Complications and Poor Outcome

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.