J. Paul Elliott

The devastating potential of blunt vertebral arterial injuries.

OBJECTIVE To formulate management guidelines for blunt vertebral arterial injury (BVI). SUMMARY BACKGROUND DATA Compared with carotid arterial injuries, BVIs have been considered innocuous. Although screening for BVI has been advocated, particularly in patients with cervical spine injuries, the appropriate therapy of lesions is controversial. METHODS In 1996 an aggressive arteriographic screening protocol for blunt cerebrovascular injuries was initiated. A prospective database of all screened patients has been maintained. Analysis of injury mechanisms and patterns, BVI grades, treatment, and outcomes was performed. RESULTS Thirty-eight patients (0.53% of blunt trauma admissions) were diagnosed with 47 BVIs during a 3.5-year period. Motor vehicle crash was the most common mechanism, and associated injuries were common. Cervical spine injuries were present in 71% of patients, but there was no predilection for cervical vertebral level or fracture pattern. The incidence of posterior circulation stroke was 24%, and the BVI-attributable death rate was 8%. Stroke incidence and neurologic outcome were independent of BVI injury grade. In patients treated with systemic heparin, fewer overall had a poor neurologic outcome, and fewer had a poor outcome after stroke. Trends associated with heparin therapy included fewer injuries progressing to a higher injury grade, fewer patients in whom stroke developed, and fewer patients deteriorating neurologically from diagnosis to discharge. CONCLUSIONS Blunt vertebral arterial injuries are more common than previously reported. Screening patients based on injury mechanisms and patterns will diagnose asymptomatic injuries, allowing the institution of therapy before stroke. Systemic anticoagulation appears to be effective therapy: it is associated with improved neurologic outcome in patients with and without stroke, and it appears to prevent progression to a higher injury grade, stroke, and deterioration in neurologic status.

Optimizing screening for blunt cerebrovascular injuries

BACKGROUND The recognition that early diagnosis and intervention, prior to ischemic neurologic injury, has the potential to improve outcome following blunt cerebrovascular injuries (BCVI), led to a policy of aggressive screening for these injuries. The resultant epidemic of BCVI has created a dilemma, as widespread screening is impractical. We sought to identify independent predictors of BCVI, to focus resources. METHODS Cerebral arteriography was performed based on signs or symptoms of BCVI, or in asymptomatic patients with high-risk mechanisms (hyperextension, hyperflexion, direct blow) or injury patterns. Logistic regression analysis identified independent predictors. RESULTS A total of 249 patients underwent arteriography; 85 (34%) had injuries. Independent predictors of carotid arterial injury were Glasgow coma score < or =6, petrous bone fracture, diffuse axonal brain injury, and LeFort II or III fracture. Having one of these factors in the setting of a high-risk mechanism was associated with 41% risk of injury. Of patients with cervical spine fracture, 39% had vertebral arterial injury. CONCLUSIONS Patients sustaining high-risk injury mechanisms or patterns should be screened for BCVI. In the face of limited resources, screening efforts should be focused on those with high-risk predictors.

Differential Gene Expression in Human Cerebrovascular Malformations

OBJECTIVEWe sought to identify genes with differential expression in cerebral cavernous malformations (CCMs), arteriovenous malformations (AVMs), and control superficial temporal arteries (STAs) and to confirm differential expression of genes previously implicated in the pathobiology of these lesions. METHODSTotal ribonucleic acid was isolated from four CCM, four AVM, and three STA surgical specimens and used to quantify lesion-specific messenger ribonucleic acid expression levels on human gene arrays. Data were analyzed with the use of two separate methodologies: gene discovery and confirmation analysis. RESULTSThe gene discovery method identified 42 genes that were significantly up-regulated and 36 genes that were significantly down-regulated in CCMs as compared with AVMs and STAs (P = 0.006). Similarly, 48 genes were significantly up-regulated and 59 genes were significantly down-regulated in AVMs as compared with CCMs and STAs (P = 0.006). The confirmation analysis showed significant differential expression (P < 0.05) in 11 of 15 genes (angiogenesis factors, receptors, and structural proteins) that previously had been reported to be expressed differentially in CCMs and AVMs in immunohistochemical analysis. CONCLUSIONWe identify numerous genes that are differentially expressed in CCMs and AVMs and correlate expression with the immunohistochemistry of genes implicated in cerebrovascular malformations. In future efforts, we will aim to confirm candidate genes specifically related to the pathobiology of cerebrovascular malformations and determine their biological systems and mechanistic relevance.

Red blood cell transfusion is associated with infection and extracerebral complications after subarachnoid hemorrhage.

OBJECTIVERed blood cell transfusion (RBCT) is associated with medical complications in general medical and surgical patients. We examined the hypothesis that RBCT during intensive care unit (ICU) care is associated with medical complications after subarachnoid hemorrhage (SAH). METHODSWe retrospectively analyzed a prospective observational database containing 421 patients with SAH (mean age, 51.5 years; standard deviation, 14.6 years). Logistic regression models were used to adjust for age, admission hemoglobin (Hgb), clinical grade, average ICU Hgb, and symptomatic vasospasm. RESULTSTwo hundred fourteen patients received an RBCT during their ICU stay. Medical complications were identified in 156 patients and were more common in those who received blood (46%) than in those who did not (29.8%) (P < .001). Major medical complications (cardiac, pulmonary, renal, or hepatic) occurred in 111 patients, and minor complications (eg, skin rash, deep vein thrombosis) occurred in 45 patients. Any non–central nervous system infection (n = 183; P < .001), including pneumonia (n = 103; P < .001) or septicemia (n = 36; P = .02), was more common with RBCT. Central nervous system infections (meningitis, cranial wound, n = 15) also were associated with RBCT (P = .03). Mechanically ventilated patients (n = 259) were more likely to have received an RBCT than those who did not (P < .001). When logistic regression was used to control for age, admission clinical grade and Hgb, average ICU Hgb, symptomatic vasospasm, and other admission variables associated with outcome, the following factors (odds ratio; 95% confidence interval) were associated with RBCT: any medical complication (1.8; 1.1–3.0), major medical complications (2.1; 1.2–3.7), any infection (2.8; 1.7–4.5), pneumonia (2.6; 1.5–4.7), septicemia (2.9; 1.2–6.8), and need for mechanical ventilation (2.8; 1.5–5.1). CONCLUSIONThese data suggest that RBCTs are associated with medical complications after SAH. However, the data do not infer causation, and further study is necessary to better define the indications for transfusion after SAH.

ENDOVASCULAR THERAPY FOR ANEURYSMAL VASOSPASM

Endovascular treatment of cerebral vasospasm induced by subarachnoid hemorrhage has become a useful therapy. The two main treatments that have been used are balloon angioplasty and intra-arterial papaverine infusion. Both treatments have been shown to reverse subarachnoid hemorrhage-induced vascular spasm, increase cerebral blood flow and improve delayed ischemic neurologic deficits induced by vasospasm. Balloon angioplasty is superior to papaverine for treatment of proximal vessel vasospasm by virtue of a more sustained effect on the vessels. Papaverine can be useful as an adjunct to balloon angioplasty and also for the treatment of distal vessels that are not accessible for balloon angioplasty.

Association of a younger age with an increased risk of angiographic and symptomatic vasospasms following subarachnoid hemorrhage

OBJECT Vasospasm is a leading cause of morbidity and death following aneurysmal subarachnoid hemorrhage (SAH). It is important to predict which patients are at risk for vasospasm so that interventions can be made. There are several potential risk factors for vasospasm, one of which is age. However, the effect of age on vasospasm, particularly symptomatic vasospasm, remains controversial. METHODS Three hundred ninety-one patients were retrospectively identified from a prospective observational database of patients with SAH who had been admitted to a single center. Demographic and clinical data were recorded, and cerebral angiograms obtained at admission and between 5 and 10 days later were compared. The relationship between age and angiographic and symptomatic vasospasms was examined using logistic regression techniques. RESULTS Mild (86 patients), moderate (69 patients), severe (56 patients), and no angiographic vasospasms (180 patients) were documented by comparing admission and follow-up angiograms in each patient. Symptomatic vasospasm was identified in 69 patients (17.6%). Angiographic vasospasm was more frequent as age decreased. Except in patients < 30 years old, the frequency of symptomatic vasospasm also increased with decreasing age (p = 0.0001). After adjusting for variables known to be associated with vasospasm, an advanced age was associated with a reduced incidence of any angiographic vasospasm (OR 0.96, 95% CI 0.94-0.97), severe angiographic vasospasm (OR 0.96, 95% CI 0.95-0.98), and symptomatic vasospasm (OR 0.98, 95% CI 0.96-0.99). CONCLUSIONS Results in this study show that a younger age is associated with an increased incidence of angiographic and symptomatic vasospasm.

Differential cerebral protein synthesis and heat shock protein 70 expression in the core and penumbra of rat brain after transient focal ischemia

OBJECTIVEThe purpose of this study was to correlate the cerebral protein synthesis (CPS) reductions in the ischemic core and penumbra with the metabolic stress response indicated by heat shock protein 70 (HSP70) synthesis. METHODSRats were subjected to 90 minutes of temporary focal cerebral ischemia produced by occlusion of the middle cerebral artery, using the endovascular suture model. Regional CPS was qualitatively evaluated, with [35S]methionine autoradiography, after reperfusion for 2 to 72 hours. The observed changes were correlated with HSP70 immunoreactivity, as assessed in the same brain sections. The ischemic core in the striatum was characterized by HSP70 expression only in endothelial and/or glial cells, with an absence of expression in neurons. The penumbra was delineated as the cortical middle cerebral artery territory region in which HSP70 was also expressed in metabolically stressed neurons. RESULTSAfter 2 hours of reperfusion, CPS was reduced to 30 ± 16% of the homologous contralateral hemisphere value in the core and to 75 ± 22% in the penumbra (P < 0.05). This difference was still present at 72 hours, when CPS values were 62 ± 21% and 98 ± 29% of the nonischemic contralateral hemisphere values in the core and penumbra, respectively (P < 0.05). CONCLUSIONPersistent inhibition of CPS in regions in which neuronal HSP70 expression is absent may distinguish core areas of infarction from penumbral regions in which neuronal HSP70 is present, which eventually recover from sublethal metabolic stress during reperfusion after temporary focal ischemia.

Comparison of balloon angioplasty and papaverine infusion for the treatment of vasospasm following aneurysmal subarachnoid hemorrhage

OBJECT The purpose of this study was to test the hypothesis that balloon angioplasty is superior to papaverine infusion for the treatment of proximal anterior circulation arterial vasospasm following subarachnoid hemorrhage (SAH). Between 1989 and 1995, 125 vasospastic distal internal carotid artery or proximal middle cerebral artery vessel segments were treated in 52 patients. METHODS Blood flow velocities of the involved vessels were assessed by using transcranial Doppler (TCD) monitoring in relation to the day of treatment with balloon angioplasty or papaverine infusion. Balloon angioplasty and papaverine infusion cohorts were compared based on mean pre- and posttreatment velocity at 24 and 48 hours using the one-tailed, paired-samples t-test. Balloon angioplasty alone was performed in 101 vessel segments (81%) in 39 patients (75%), whereas papaverine infusion alone was used in 24 vessel segments (19%) in 13 patients (25%). Although repeated treatment after balloon angioplasty was needed in only one vessel segment, repeated treatment following papaverine infusion was required in 10 vessel segments (42%) in six patients because of recurrent vasospasm (p < 0.001). Seven vessel segments (29%) with recurrent spasm following papaverine infusion were treated with balloon angioplasty. Although vessel segments treated with papaverine demonstrated a 20% mean decrease in blood flow velocity (p < 0.009) on posttreatment Day 1, velocities were not significantly lower than pretreatment levels by posttreatment Day 2 (p = 0.133). Balloon angioplasty resulted in a 45% mean decrease in velocity to a normal level following treatment (p < 0.001), a decrease that was sustained. CONCLUSIONS Balloon angioplasty is superior to papaverine infusion for the permanent treatment of proximal anterior circulation vasospasm following aneurysmal SAH.