Intraarterial Infusion of Papaverine in Experimental Cerebral Vasospasm—Fujiwara N (1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-07, Japan), Honjo Y, Ohkawa M, Tanabe M, Irie K, Nagao S, Takashima H, Satoh K, Kojima K—Am J Neuroradiol. 1997;18:255-262.
Purpose: To determine the effectiveness of intraarterial infusion of papaverine hydrochloride (PPV) in an experimental model of cerebral vasospasm and to measure the mean blood flow velocity of the middle cerebral artery (MCA). Methods: Seven Japanese monkeys were divided into three groups: those studied 3 days after surgery (the third-day group, n=3); those studied 7 days after surgery (the seventh-day group, n=3); and a control group (n=1). Vasospasm was induced in the experimental groups by placing a blood clot in the subarachnoid space around the top of the internal carotid siphon. PPV (5 mg/kg) was infused (over 60 minutes) into the internal carotid artery (ICA). The vascular diameters of the ICA and MCA were measured on angiograms before and after infusion. The mean blood flow velocity in the MCA was measured on transcranial Doppler sonograms before and 24 hours after infusion. After fixation, the MCA was dissected out, stained, and examined microscopically. Results: After vasospasm induction, both arteries were narrowed more than 30% in the third-day group and more than 50% in the seventh-day group. After PPV infusion in both groups, vascular dilatation of about 20% was seen. The mean increase in blood flow velocity in the third-day group (30%) was smaller than in the seventh-day group (70%). The mean blood flow velocity in the MCA decreased by about 30% in both groups, but increased again after 24 hours nearly to the level before PPV infusion. The intimal layer was more corrugated in the seventh-day group, and hypertrophy in the smooth muscle layer was also seen. Clinical examination showed no neurologic deficit in the third-day group 24 hours after PPV infusion; neurologic deficits were observed in the seventh-day group. Conclusion: PPV infusion may be more effective in early stages of vasospasm when vascular walls have fewer histologic changes.
Key Words: cerebral aneurysm, vasospasm
Serial Changes of Hemostasis in Aneurysmal Subarachnoid Hemorrhage With Special Reference to Delayed Ischemic Neurologic Deficits—Fujii Y (Dept of Neurosurgery, Brain Research Institute, Niigata University, Asahimachi 1, Niigata 951, Japan), Takeuchi S, Sasaki O, Minakawa T, Koike T, Tanaka R—J Neurosurg. 1997;86:594-602.
This study was undertaken to elucidate comprehensively the serial changes occurring in hemostatic systems after aneurysmal subarachnoid hemorrhage (SAH) and thereby to ascertain whether the examination of the integrity of these systems is helpful in predicting delayed ischemic neurological deficits (DINDs). The authors examined 117 patients admitted to the hospital within 24 hours after onset of SAH. Blood samples were collected from each patient on Days 0 (at admission), 3, 6, 14, and 30. A number of hemostatic parameters were examined in these samples, and the relationships between their changes and DINDs were assessed. Eighteen (15.4%) of the patients exhibited DINDs, and their frequency increased as the severity of subarachnoid clotting increased. Also, the frequency of DINDs was significantly higher in the patients with hydrocephalus on initial computerized tomography (CT) scans than in those without hydrocephalus. Regarding the hemostatic parameters at admission, there was no significant difference between the patients with and without DINDs. On Day 3, however, the fibrinogen and D-dimer levels were higher in the patients with than in those without DINDs. The fibrinogen and thrombin–antithrombin complex levels on Day 6 and the D-dimer level on Day 14 in the patients with DINDs were higher than the corresponding levels in those without DINDs. Multivariate analyses revealed that the following variables (in order of importance) were independent predictors of DINDs: the levels of D-dimer on Day 3, fibrinogen on Day 6, and the presence of hydrocephalus on admission. These data indicate that the levels of hemostatic parameters in concert with the CT findings may enable us to predict the appearance of DINDs.
Key Words: subarachnoid hemorrhage, blood coagulation
Subacute and Chronic Subarachnoid Hemorrhage: Diagnosis With Fluid-Attenuated Inversion-Recovery MR Imaging—Noguchi K, Ogawa T, Seto H, Inugami A, Hadeishi H, Fujita H, Hatazawa J, Shimosegawa E, Okudera T, Uemura K—Radiology. 1997;203:257-262.
Purpose: To evaluate fluid-attenuated inversion-recovery (FLAIR) magnetic resonance (MR) imaging in the detection of subacute and chronic subarachnoid hemorrhage.
Materials and Methods: The authors performed 19 FLAIR MR imaging examinations at 0.5 T in 14 adult patients with subarachnoid hemorrhage 3–45 days after the ictus and 22 FLAIR examinations in 22 adult control subjects. The detection of subacute and chronic subarachnoid hemorrhage on FLAIR images was compared with the detection on conventional spin-echo MR and computed tomographic (CT) images.
Results: In the detection of subacute subarachnoid hemorrhage, FLAIR (100% detection) was significantly superior to T1-weighted imaging (36% detection, P<.01), T2-weighted imaging (0% detection, P<.02), and CT (45% detection, P<.02 [Fisher exact test]). Although FLAIR imaging (63% detection) was superior in chronic subarachnoid hemorrhage detection, there were no statistically significant differences between modalities. FLAIR imaging demonstrated all subarachnoid hemorrhage areas as high-signal-intensity areas within 18 days and up to a maximum of 45 days after the ictus. In a blind comparison, no FLAIR images acquired in control subjects were confused with those acquired in patients.
Conclusion: FLAIR diagnostic images are superior to conventional MR or CT images in patients with subacute subarachnoid hemorrhage.
Key Words: subarachnoid hemorrhage, magnetic resonance imaging
Cerebral Blood Flow/Metabolism
Crossed Cerebellar Diaschisis After Middle Cerebral Artery Infarction—De Reuck J (Dept of Neurology, University Hospital, De Pintelaan 185, B 9000 Ghent, Belgium), Decoo D, Lemahieu I, Strijckmans K, Goethals P, Van Maele G—Clin Neurol Neurosurg. 1997;99:11-16.
It is unclear whether crossed cerebellar diaschisis (CCD) is merely an epiphenomenon, as its clinical significance remains uncertain. We retrospectively analysed the positron emission tomographic (PET) findings in 28 patients with a chronic, stable middle cerebral artery (MCA) infarct and in 22 controls, using the steady state technique and 15O. Also, the Orgogozo scores on admission and at the time of the PET examination were compared in the patients with MCA infarction. Based on the asymmetry index and the 95% confidence limits for regional cerebellar blood flow (rCBF) and oxygen consumption (rCMRO2) in the control group, the stroke patients were subdivided in a group with (n=8) and a group without (n=20) CCD. The CCD group had lower values of rCMRO2 in the infarct and border areas compared to those of the non-CCD patients. The infarct location within the MCA territory was similar but the size was somewhat larger in the CCD group. The degree of neurological improvement was better in the non-CCD group. Although persistence of CCD has no real clinical significance it appears to be correlated to more severe and widespread ischaemia in the affected MCA territory and to the lack of significant clinical improvement.
Key Words: stroke, ischemic, diaschisis
Speech-Induced Cerebral Metabolic Activation Reflects Recovery From Aphasia—Heiss W-D (Max-Planck-Institut für neurologische Forschung, Gleueler Str 50, D-50931 Köln, Germany), Karbe H, Weber-Luzenburger G, Herholz K, Kessler J, Pietrzyk U, Pawlik G—J Neurol Sci. 1997;145:213-217.
Six stroke patients with clinically significant aphasia were studied 4 weeks and again 12–18 months after their first left hemispheric ictus. The regional cerebral metabolic rate of glucose (rCMRglc) was measured repeatedly by PET at rest and during word repetition, and severity of speech impairment was assessed by a neuropsychologic test battery. The patterns of speech-associated activation of glucose metabolism were related to improvement in language performance as measured by the Token test. Three patients experienced significant recovery from aphasia (Token test: 47 to 3, 45 to 12, and 37 to 5 points, respectively), whereas 3 patients had poor outcome (Token test: from 48 to 45, and from 47 to 39 and 24, respectively). Good recovery was related to activation of left hemispheric speech areas surrounding the infarct, especially left superior temporal gyrus. In contrast, the 3 patients with persistent aphasia showed rCMRglc recruitment in right hemispheric regions and were unable to activate left hemispheric speech areas on follow-up. These results indicate that favorable outcome is related to partial sparing of speech areas of the dominant hemisphere that can be (re-)activated. Predominant recruitment of contralateral areas is not efficacious for a considerable recovery from aphasia. It rather indicates unspecific involvement of widespread networks in the effort to perform a complex task.
Key Words: cerebral metabolism, stroke outcome
Lipoprotein Oxidation and Progression of Carotid Atherosclerosis—Salonen JT (Research Institute of Public Health, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland), Nyyssönen K, Salonen R, Porkkala-Sarataho E, Tuomainen T-P, Diczfalusy U, Björkhem I—Circulation. 1997;95:840-845.
Background Epidemiological studies and animal experiments have provided evidence supporting the role of lipid peroxidation in atherogenesis and cardiovascular diseases. Direct evidence linking lipid oxidation to atherosclerotic progression in humans, however, has been lacking. We investigated the association of lipid oxidation products with the progression of early carotid atherosclerosis in hypercholesterolemic men from eastern Finland.
Methods and Results Twenty subjects with a fast progression and 20 with no progression of carotid atherosclerosis in 3 years were selected from >400 participants in the Kuopio Atherosclerosis Prevention Study. Progression of carotid atherosclerosis was assessed by high-resolution B-mode ultrasonography. Serum 7β-hydroxycholesterol, a major oxidation product of cholesterol in membranes and lipoproteins, and seven other cholesterol oxidation products were measured by isotope dilution–mass spectrometry, lipid hydroperoxides in LDL fluorometrically as thiobarbituric acid–reactive substances (TBARS) and oxidation susceptibility of LDL and VLDL kinetically. High concentrations of serum 7β-hydroxycholesterol (β=.47, P=.0005), cigarette smoking (β=.35, P=.0167), and LDL TBARS (β=.23, P=.0862) and an increased oxidation susceptibility of VLDL+LDL (β=.22, P=.1114) were the strongest predictors of a 3-year increase in carotid wall thickness of more than 30 variables tested in step-up least-squares regression models. A 10-variable model explained 60% of the atherosclerotic progression. In a multivariate logistic model, the risk of experiencing a fast progression increased by 80% (P=.013) per unit (μg/L) of 7β-hydroxycholesterol.
Conclusions The findings of this study provide further evidence to support an association between lipid oxidation and atherogenesis in humans.
Key Words: atherosclerosis, lipoproteins
Patients With Stroke Confined to Basal Ganglia Have Diminished Response to Rehabilitation Efforts—Miyai I, Blau AD, Reding MJ, Volpe BT (Dept of Neurology, Cornell University Medical College, The Burke Rehabilitation Center, 785 Mamaroneck Ave, White Plains, NY 10605—Neurology. 1997;48:95-101.
Prediction of the functional outcome for patients with stroke has depended on the severity of impairment, location of brain injury, age, and general medical condition. This study compared admission and discharge functional outcome (Functional Independence Measure, FIM) and deficit severity (Fugl-Meyer, F-M) scores in a retrospective study of patients with similar neurologic impairments: homonymous hemianopia, hemisensory loss, and hemiparesis. CT-verified stroke location was the independent variable: cortical (n=11), basal ganglia and internal capsule (normal cortex and thalamus, n=13), or combined (cortical, basal ganglia, and internal capsule, n=22). By 3 months on average after stroke, all groups demonstrated significantly improved motor function as measured by F-M scores. Patients with cortical lesions had the least CT-imaged damage and the best outcome. Patients with combined lesions and more extensive brain injury had significantly higher FIM scores (p<0.05) than patients with injury restricted to the basal ganglia/internal capsule. Patients with basal ganglia/internal capsule injury were more likely to have hypotonia, flaccid paralysis, and persistently impaired balance and ambulation performance. While all patients had a comparable rehabilitation experience, these results suggest that patients with stroke confined to the basal ganglia and internal capsule benefited less from therapy. Isolated basal ganglia stroke may cause persistent corticothalamic-basal ganglia interactions that are dysfunctional and impede recovery.
Key Words: stroke outcome, rehabilitation
Hypertension and Borderline Isolated Systolic Hypertension Increase Risks of Cardiovascular Disease and Mortality in Male Physicians—O’Donnell CJ (Framingham Heart Study, 5 Thurber St, Framingham, MA 01701), Ridker PM, Glynn RJ, Berger K, Ajani U, Manson JE, Hennekens CH—Circulation. 1997;95:1132-1137.
Background The objective of this study was to examine whether definite hypertension and borderline isolated systolic hypertension predict subsequent cardiovascular disease and mortality.
Methods and Results This was a prospective cohort study with a mean follow-up of 11.7 years. The subjects were a group of 18 682 apparently healthy US men, aged 40 to 84 years, participating in the Physicians’ Health Study, a randomized trial of low-dose aspirin and β-carotene. The main outcome measures were total cardiovascular disease, myocardial infarction, stroke, cardiovascular death, and all-cause mortality. Hypertension was associated with substantially increased risks of total cardiovascular disease (relative risk [RR] 1.92; 95% confidence interval [CI], 1.70 to 2.18), myocardial infarction (RR, 1.78; 95% CI, 1.49 to 2.13), stroke (RR, 2.19; 95% CI, 1.78 to 2.69), and cardiovascular death (RR, 2.10; 95% CI, 1.68 to 2.63). Borderline isolated systolic hypertension was associated with significantly increased risks of cardiovascular disease (RR, 1.32; 95% CI, 1.09 to 1.59), stroke (RR, 1.42; 95% CI, 1.04 to 1.93), and cardiovascular death (RR, 1.56; 95% CI, 1.13 to 2.15), as well as a possible but nonsignificant increased risk of myocardial infarction (RR, 1.26; 95% CI, 0.95 to 1.67). Hypertension and borderline isolated systolic hypertension were associated with significantly increased risks of 41% and 22%, respectively, for all-cause mortality.
Conclusions Hypertension as well as borderline isolated systolic hypertension are associated with elevated risks of cardiovascular diseases, especially stroke and cardiovascular death. Hypertension is associated with an increased risk of myocardial infarction, and borderline isolated systolic hypertension predicts a possible but more modest increase in risk. These data add to the existing evidence that hypertension is a major cardiovascular risk factor and extend the findings to borderline isolated systolic hypertension.
Key Words: hypertension, arterial occlusive disease
Ethnic Distribution of Factor V Leiden in 4047 Men and Women: Implications for Venous Thromboembolism Screening—Ridker PM (Brigham and Women’s Hospital, 900 Commonwealth Ave E, Boston, MA 02215-1204), Miletich JP, Hennekens CH, Buring JE—JAMA. 1997;277:1305-1307.
Objective.—To estimate ethnic-specific prevalence rates of factor V Leiden, an inherited defect of hemostasis associated with risk of venous thrombosis.
Design.—Survey of 4047 American men and women participating in the Physicians’ Health Study (PHS) or in the Women’s Health Study (WHS). All study participants were free of myocardial infarction, stroke, or venous thrombosis.
Main Outcome Measure.—Prevalence of G1691A Leiden mutation in the gene coding for coagulation factor V was determined in the PHS group using polymerase chain reaction techniques and, in the WHS group, a second-generation activated protein C (APC)–resistance screening test with genetic confirmation of all borderline and low-value results.
Results.—In 2468 Caucasian Americans, carrier frequency of factor V Leiden was 5.27% (95% confidence interval [CI], 4.42%-6.22%). Carrier frequency was 2.21% in 407 Hispanic Americans, 1.23% in 650 African Americans, 0.45% in 442 Asian Americans, and 1.25% in 80 Native Americans. Thus, prevalence of factor V Leiden was less among minority subjects (P=.001). Carrier frequencies were similar in Caucasian men and women (5.53% vs 4.85% respectively, P=.5).
Conclusion.—These data indicate that prevalence of factor V Leiden is greater among Caucasians than minority Americans. These data have implications for clinicians considering whether to screen for factor V Leiden in high-risk groups such as those with prior venous thromboses or coexistent defects of anticoagulation and women at risk for postpartum thrombosis or seeking oral contraceptives.
Key Words: thrombosis, ethnic group
Antithrombotic Potency of Hirudin Is Increased in Nonhuman Primates by Fibrin Targeting—Bode C, Hanson SR, Schmedtje JF, Haber E, Mehwald P, Kelly AB, Harker LA, Runge MS (Div of Cardiology, University of Texas Medical Branch, 301 University Blvd, Route 0553, Galveston, TX 77555-0553)—Circulation. 1997;95:800-804.
Background Inhibition of thrombin by either the indirect thrombin inhibitor heparin or by more potent direct thrombin inhibitors such as hirudin reduces thrombus formation after arterial injury. The present study was designed to determine if a fibrin-specific thrombin inhibitor could, by local thrombin inhibition, prevent thrombosis more effectively.
Methods and Results We first studied antithrombotic potency in vitro, comparing fibrin-targeted hirudin (recombinant hirudin covalently linked to the Fab′ fragment of the anti-fibrin monoclonal antibody 59D8) to recombinant hirudin in baboon plasma. Fibrin-targeted hirudin was nine times more effective than recombinant hirudin in inhibiting fibrin deposition on experimental clot surfaces in baboon plasma (P<.01). The potency of fibrin-targeted hirudin was then compared with that of recombinant hirudin in a baboon model of thrombus formation. 111In-labeled platelet deposition was measured in a synthetic graft segment of an extracorporeal arteriovenous shunt in control animals and in animals receiving either fibrin-targeted hirudin or hirudin. In these experiments, fibrin-targeted hirudin was 10-fold more potent than hirudin in inhibiting platelet deposition and thrombus formation (P<.05).
Conclusions These data indicate that targeting a thrombin inhibitor such as hirudin to an epitope present in thrombi results in increased antithrombotic potency.
Key Words: thrombosis, thrombin
Increased Hypoxic Tolerance by Chemical Inhibition of Oxidative Phosphorylation: “Chemical Preconditioning”—Riepe MW (Dept of Neurology, University of Ulm, Steinhövelstr 9, 89075 Ulm, Germany), Esclaire F, Kasischke K, Schreiber S, Nakase H, Kempski O, Ludolph AC, Dirnagl U, Hugon J—J Cereb Blood Flow Metab. 1997;17:257-264.
A short ischemic episode preceding sustained ischemia is known to increase tolerance against ischemic cell death. We report early-onset long-lasting neuroprotection against in vitro hypoxia by preceding selective chemical inhibition of oxidative phosphorylation: “chemical preconditioning.” The amplitude of CA1 population spikes (psap) in hippocampal slices prepared from control animals (control slices) was 31±27% (mean±SD) upon 45-min recovery from 15-min in vitro hypoxia. In slices prepared from animals treated in vivo with 20 mg/kg 3-nitropropionate (3-np) 1–24 h prior to slice preparation (preconditioned slices), psap improved to 90±15% (p<0.01). Posthypoxic oxygen free radicals were reduced to 65±10% (mean±SD) of control in preconditioned slices (p<0.05). Posthypoxic neuronal density improved from 52±15% (mean±SD) in control slices to 97±23% in preconditioned slices (p<0.001). Glibenclamide, an antagonist at KATP-channels, partly reversed increased hypoxic tolerance. We conclude that chemical preconditioning induces early-onset long-lasting tolerance against in vitro hypoxia. Ultimately, this strategy may be applicable as a neuroprotective strategy in humans.
Key Words: cerebral ischemia, hypoxia
Neuroprotective Effect of NMDA Receptor Glycine Recognition Site Antagonism Persists When Brain Temperature Is Controlled—Takaoka S, Bart RD, Pearlstein R, Brinkhous A, Warner DS (Dept of Anesthesiology, Box 3094, Duke University Medical Center, Durham, NC 27710)—J Cereb Blood Flow Metab. 1997;17:161-167.
Several lines of inquiry have indicated that glycine plays an important role in both glutamatergic neurotransmission and pathophysiology of cerebral ischemia. However, subacute outcome trials demonstrating the efficacy of glycine antagonists as neuroprotectants have not been performed with rigorous control of brain temperature. In this study, we investigated the effect of N-methyl-d-aspartate (NMDA) receptor glycine recognition site antagonism in a temperature-controlled rodent model of transient focal ischemia. Male Wistar rats underwent 75 min of intraluminal middle cerebral artery occlusion (MCAO). During MCAO and the first 24 h of reperfusion, rats (n=10) were administered either vehicle or the glycine antagonist 5-nitro-6,7-dichloro-2,3-quinoxalinedione (ACEA 1021) i.v. as a bolus infusion of 5 mg/kg followed by 3.5 mg/kg/h (Low-Dose) or 10 mg/kg followed by 7 mg/kg/h (High-Dose) for 24 h. Cortical temperature was controlled at 38.0±0.1°C during MCAO and the first 6 h of reperfusion. A 7-day recovery interval was allowed. Mean total infarct volume was reduced by ≈40% in both high- and low-dose groups (p<0.01). The preponderance of infarct reduction occurred in the cortex (p<0.01). Neurologic function correlated with the size of cerebral infarct (p=0.001). Neurologic grade was similarly improved by treatment with either dose (p=0.01). These results demonstrate that neuroprotection achieved by antagonism of the glycine recognition site persists when brain temperature is controlled, indicating a potent mechanism of action other than attenuating a hyperthermic response to ischemia.
Key Words: neuroprotection, calcium channel blockers
Chronic Nicotine Treatment Enhances Focal Ischemic Brain Injury and Depletes Free Pool of Brain Microvascular Tissue Plasminogen Activator in Rats—Wang L, Kittaka M, Sun N, Schreiber SS, Zlokovic BV (2025 Zonal Ave, RMR 506, Los Angeles, CA 90033—J Cereb Blood Flow Metab. 1997;17:136-146.
Effects of nicotine treatment (4.5 mg/kg of nicotine-free base/day administered s.c. by osmotic minipumps for 14 days) on focal ischemic stroke and expression of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in cerebral microvessels were studied in rats in vivo using a reversible (1 h) middle cerebral artery occlusion model. Plasma levels of nicotine and its major metabolite cotinine after 14 days of treatment were 88 and 364 ng/ml, respectively. Nicotine treatment resulted in 35–40% (p<0.001) decrease in the blood flow in the periphery of the ischemic core during reperfusion, an increase in the neurologic score of 2.6-fold (p<0.01), and 36% (p<0.05) and 121% (p<0.01) increases in the injury and edema volume in the pallium, respectively. A free pool of brain microvascular t-PA antigen was completely depleted by nicotine, while the expression of the PAI-1 antigen and/or PAI-1–t-PA complexes remained unchanged. The relative abundance of cerebromicrovascular t-PA mRNA transcript versus β-actin mRNA transcript did not change with nicotine. It is concluded that chronic nicotine treatment impairs the restoration of blood flow, worsens the neurologic outcome, and enhances brain injury following an ischemic insult. These nicotine effects are associated with depletion of brain microvascular t-PA antigen.
Key Words: cerebral ischemia, nicotine
Correlation Between Venous Stump Pressure and Brain Damage After Cortical Vein Occlusion: An Experimental Study—Yoshimoto Y (Dept of Neurosurgery, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Shimotsuga, Tochigi 321-02, Japan), Endo M, Mori T, Wakai S—J Neurosurg. 1997;86:694-698.
A canine model of cortical vein occlusion was used to evaluate whether data obtained from monitoring venous stump pressure could help predict cerebral infarction after venous obstruction. Following bilateral parasagittal craniotomy, the cortical vein in each hemisphere was temporarily occluded and the increase in pressure was directly measured. Permanent venous obstruction was subsequently produced, and parenchymal brain damage 24 hours later was classified as: Stage 0, no parenchymal damage; Stage I, mild edema; Stage II, moderate parenchymal edema and/or ischemic changes in neurons; and Stage III, moderate-to-severe hemorrhage. The histological stages correlated closely with the rise in venous pressure: mean pressure increases (±standard deviation) were 5.5±2.9 mm Hg in hemispheres graded as Stage 0 (12 hemispheres), 7.7±3.2 mm Hg in those graded as Stage I (five), 11.2±4.1 mm Hg in those classed as Stage II (five), and 16.4±5 in those categorized as Stage III (seven). There were significant differences between Stages 0 and II (p<0.01) and between Stages 0 and III (p<0.001). Disruption of the blood-brain barrier as indicated by extravasation of Evans blue dye correlated well with the pressure increment. These results may indicate the threshold for injury after cortical venous occlusion. Venous stump pressure measurements obtained during a test occlusion may be a useful adjunct in predicting brain damage and may be helpful for intraoperative vessel selection for venous resection.
Key Words: cerebral veins, stroke outcome
Antagonism of Leukocyte Adherence by Synthetic Fibronectin Peptide V in a Rat Model of Transient Focal Cerebral Ischemia—Yanaka K, Camarata PJ (Neurology/Neurosurgery, PC, 4440 Broadway, Kansas City, MO 64111), Spellman SR, McCarthy JB, Furcht LT, Low WC—Neurosurgery. 1997;40:557-564.
Objective: Activated polymorphonuclear leukocytes (PMNs) seem to be directly involved in potentiating ischemic brain injury. Recent work in our laboratory demonstrated that synthetic fibronectin peptides significantly inhibit PMN accumulation in ischemic tissue, reduce the size of infarction, and reduce neurological dysfunction after transient focal cerebral ischemia in rats. The purpose of this study was to examine any dose-related effects (Experiment 1) and the optimal timing of the administration (Experiment 2) of synthetic fibronectin peptide V (FN-C/H-V) to further substantiate the role of the peptide in ameliorating cerebral ischemic damage.
Methods: Fifty-six animals were included in the study. We evaluated the efficacy of FN-C/H-V on PMN accumulation in ischemic tissue, infarct size, and neurological outcomes in rats subjected to 1 hour of cerebral ischemia and 48 hours of reperfusion.
Results: In Experiment 1, the animals receiving FN-C/H-V at a dose of 10 to 15 mg/kg of body weight per injection showed significant reduction of PMN accumulation, reduction of infarct size, and improvement of neurological outcomes at 48 hours after reperfusion compared to untreated animals (P<0.05). In Experiment 2, the animals receiving FN-C/H-V within 3 hours after reperfusion also showed significantly better results than untreated animals (P<0.05). Despite the treatment delay, the administration of FN-C/H-V inhibited PMN accumulation after reperfusion but did not reduce the size of infarction when administered 6 hours after reperfusion.
Conclusion: These data suggest that relatively late postischemic administration of FN-C/H-V is effective in brain protection after ischemia/reperfusion.
Key Words: cerebral ischemia, leukocytes
Age-Related Changes in Cerebral MR Angiography—Kajiya Y (Dept of Radiology, Faculty of Medicine, Kagoshima University, 8-35-1, Sakuragaoka, Kagoshima 890, Japan), Kajiya Y, Nakajo M—J Neurol Sci. 1997;145:195-203.
Two hundred forty four neurologically normal subjects (118 males and 126 females, aged 7 to 82 yrs.) were evaluated to assess the correlation of the degree of visualization of cerebral arteries on magnetic resonance angiography (MRA) with aging, sex, laterality or lacunar infarctions on magnetic resonance imaging (MRI). A single volume three-dimensional transformation time-of-flight pulse sequence with slab thickness of 115 mm was used to obtain axial, saggital and coronal projection images. A total of 6 arteries including bilateral anterior cerebral arteries (ACAs), middle cerebral arteries (MCAs) and posterior cerebral arteries (PCAs) for every subject were each graded into 8 scores by the degree of visualization of the arteries. Results show that an age-related decline of visualization of the cerebral arteries in ACA (r=−0.603, p<0.001), MCA (r=−0.452, p<0.001) and PCA (r=−0.537, p<0.001). The arteries were better visualized in females than males during the fifth decade (p<0.01). No substantial relationship was observed between the visualization and sex in the other decades, laterality or lacunar infarctions. Thus, the cerebral MRA showed an age-related decline of visualization of the arteries and a sex-difference of the visualization in the fifth decade, probably due to the decline of the blood flow velocity with aging and a difference in it between females and males in the fifth decade.
Key Words: aging, angiography, magnetic resonance
Quantitative Magnetic Resonance Analysis in Vascular Dementia—Giubilei F (Dipt Scienze Neurologiche, Viale Dell’Università 30, I-00185 Rome, Italy), Bastianello S, Paolillo A, Gasperini C, Tisei P, Casini AR, Gragnani A, Bozzao L, Fieschi C—J Neurol. 1997;244:246-251.
The potential role of magnetic resonance imaging (MRI) in differentiating between specific causes of cognitive decline in patients with vascular dementia (VD) has not yet been fully established. We therefore decided to assess the supratentorial cerebral contents in 24 patients with a diagnosis of probable VD and in 24 normal subjects, matched for age and education level, using MRI volumetric parameters obtained by means of a quantitative method. The volumes of subarachnoid and ventricular spaces, cerebral tissue, and hyperintense areas on T2-weighted images were calculated. In order to reduce interindividual variability caused by differences in intracranial size, each absolute measurement was normalized to the relative size of the intracranial volume. In addition, we calculated the ratio between the areas of the corpus callosum (CC) and supratentorial brain at the same level on the T1-weighted image midsagittal plane. The MRI data were correlated with the deterioration of cognitive functions. Patients with VD showed significantly lower cerebral tissue volume and CC area, and higher ventricular space volume than normal subjects. Furthermore, the total volume of the T2 signal alterations was higher in VD patients than in normal subjects. In VD patients, this volume was found to be proportional to the increase in the volume of the ventricular space. On the other hand, no correlation was found between the volume of the T2 signal alterations and the area of the CC. The degree of global cognitive dysfunction and the score of each neuropsychological test did not show any correlation with the MRI data. Our results suggest that ventricular enlargement in VD patients is correlated with the increase in volume of the T2 signal abnormalities, but that the degree of global cognitive dysfunction is not influenced by the volume of these T2 signal abnormalities. Furthermore, the CC atrophy does not influence the score of any neuropsychological test or the degree of global cognitive dysfunction.
Key Words: multi-infarct dementia, magnetic resonance imaging
Magnetic Resonance Angiography of the Aortic Arch—Carpenter JP (Hospital of the University of Pennsylvania, 3400 Spruce St, Philadelphia, PA 19104), Holland GA, Golden MA, Barker CF, Lexa FJ, Gilfeather M, Schnall MD—J Vasc Surg. 1997;25:145-151.
Duplex ultrasound and magnetic resonance angiographic (MRA) studies are the principal noninvasive methods for evaluation of extracranial occlusive disease in patients at risk for stroke, but each has limited ability to diagnose aortic arch and arch vessel disease. Recent favorable reports of the nonnephrotoxic contrast agent Gadolinium (Gd) being used to enhance MRA images of the abdominal aorta prompted us to examine its utility for the aortic arch vessels. Prospectively, 28 patients with suspected carotid or arch vessel disease were imaged by contrast arteriographic examination and MRA+Gd of the aortic arch within 30 days of each other. One (for contrast arteriograms) or two (for MRA) blinded readers measured stenoses with the contrast arteriograms as the standard. A total of 196 arch vessels containing 58 stenoses and four occlusions (by arteriogram) were examined with each method. Interobserver agreement for interpretation of MRA studies was substantial (κ=0.68). MRA detected all anatomic anomalies (e.g., bovine arch). The correlation of MRA with arteriographic scans for arch vessel stenoses >50% was sensitivity, 73% (readers 1 and 2); specificity, 98% (reader 1), 89% (reader 2); positive predictive value, 73% (reader 1), 89% (reader 2); negative predictive value, 98% (readers 1 and 2); accuracy, 97% (reader 1), 98% (reader 2). MRA+Gd is an accurate new noninvasive imaging method for detection of significant aortic arch disease. In its current state of development, however, it cannot obviate the need for contrast arteriographic examination.
Key Words: aortic arch, angiography, magnetic resonance
Variation of Common Carotid Artery Elasticity With Intimal-Medial Thickness: The ARIC Study—Riley WA (Dept of Neurology, Bowman Gray School of Medicine, Winston-Salem, NC 27157-1078), Evans GW, Sharrett AR, Burke GL, Barnes RW—Ultrasound Med Biol. 1997;23:157-164.
The Atherosclerosis Risk in Communities (ARIC) study is a prospective investigation of the etiology and natural history of atherosclerosis and cardiovascular disease in four U.S. communities. The purpose of this work is to investigate the relationship between common carotid artery elasticity and intimal-medial thickness (IMT) in the four race-gender groups represented in the ARIC cohort. Noninvasive ultrasonic methods were used to measure IMT and the [systolic minus diastolic] diameter change (DC) of the left common carotid artery in 10,920 black and white, men and women between the ages of 45 and 64 y. The relationship between DC and IMT and IMT2 was examined after adjustment of DC for age, height, diastolic diameter, diastolic blood pressure and linear and quadratic terms for pulse pressure. This adjusted value of DC was used as an index of elasticity of the common carotid artery in the ARIC cohort with larger values of adjusted DC implying a more elastic vessel. The general behavior of adjusted DC with increasing IMT was observed to be qualitatively similar in all four race-gender groups. Adjusted DC remained nearly constant or increased slightly for values of IMT between approximately 0.4 and 0.8 mm, up to approximately the 90th percentile of IMT, and then decreased above the 90th percentile of IMT. Common carotid artery elasticity, defined as adjusted DC, varies with increasing IMT in the ARIC cohort in a manner consistent with results from previous studies in animals and human subjects addressing the variation of several elasticity indices with atherosclerotic involvement and risk factor exposure in the aorta, and brachial and radial arteries. Our results suggest that thicker common carotid artery walls in middle-aged U.S. populations are no stiffer than thinner walls, except for the thickest 10% of arteries. Since the distal common carotid artery frequently contains atheromatous plaques in this population, the lack of change in stiffness, indeed, the reduction in stiffness per unit thickness, may reflect the various stages of early common carotid atherosclerosis most often found in this population. These are characterized more by destruction of arterial wall structural elements than by changes such as widespread or circumferential sclerosis, which would strengthen and stiffen the artery.
Key Words: carotid artery diseases, atherosclerosis
Characterisation of Atherosclerotic Plaque by Spectral Analysis of Intravascular Ultrasound: An In VitroMethodology—Spencer T (Dept of Medical Physics [OPD], Western General Hospital, Crewe Rd, Edinburgh EH4 2XU, Scotland), Ramo MP, Salter DM, Anderson T, Kearney PP, Sutherland GR, Fox KAA, McDicken WN—Ultrasound Med Biol. 1997;23:191-203.
Raw 30-MHz intravascular ultrasound data have been captured from postmortem coronary arteries (n=4) to develop radio frequency analysis techniques for the characterisation of atherosclerotic plaque. Digitised data acquired from positions (n=8) within diseased sections of artery were compared with the corresponding histology and radiology. Scan-converted images were used to locate regions of interest (ROI=33) within areas of known tissue composition: loose fibrotic tissue (LFT), dense fibrotic tissue (DFT) and calcium (CA). A range of parameters was extracted from the normalised power spectrum of each ROI within the bandwidth 17–42 MHz. Significant discrimination between LFT/DFT and between LFT/CA was provided by maximum power and spectral slope (dBMHz−1). However, the greatest discriminative power was given by the y-axis (0 Hz) intercept of the spectral slope: LFT/DFT (p=0.001); LFT/CA (p=0.0001); and DFT/CA (p=0.089).
Key Words: atherosclerosis, ultrasonics
Elective Stenting of the Extracranial Carotid Arteries—Yadav JS, Roubin GS (Interventional Cardiovascular Section, Boshell Diabetes Bldg, Seventh Ave S, University of Alabama at Birmingham, Birmingham, AL 35294-0012), Iyer S, Vitek J, King P, Jordan WD, Fisher WS—Circulation. 1997;95:376-381.
Background Surgical endarterectomy has been shown to be superior to medical management in the management of severe carotid stenosis in both symptomatic and asymptomatic patients. Endarterectomy, although effective, does have limitations, and percutaneous techniques may offer an alternative method of treatment.
Methods and Results The feasibility and safety of percutaneous carotid angioplasty and elective (primary) stenting was evaluated prospectively in a consecutive series of 107 patients. One hundred twenty-six carotid arteries with significant stenosis were treated. This series represented a high-risk subset that included patients with previous ipsilateral endarterectomy and severe medical comorbidity. Forty-five percent of the patients were referred by surgeons. Patients had independent neurological examinations before and after the procedure and follow-up cerebral angiography at 6 months. The mean (±SD) stenosis was reduced from 78±14% to 2±5%. There were 7 minor strokes, 2 major strokes, and 1 death during the initial hospitalization and first 30 days after the procedure. For the combined end point of all strokes and death, the incidence was 7.9%. For ipsilateral major stroke and death, the incidence was 1.6%. There were no strokes during the follow-up period. Mean angiographic stenosis at 6 months in 81 patients was 18±16% (range, −21% to 57%). Four (4.9%) of these 81 patients had asymptomatic restenosis. Five asymptomatic patients had repeat intervention: 2 had angioplasty for restenosis, 2 had angioplasty for stent deformation, and 1 had endarterectomy for restenosis.
Conclusions In a high-risk group of patients, percutaneous carotid angioplasty and stenting are feasible and can be performed with low restenosis and repeat intervention rates.
Key Words: carotid artery diseases, stents
Early Outcome in Acute Ischemic Stroke Is Not Influenced by the Prophylactic Use of Low-Dose Aspirin—De Keyser J (Dept of Neurology, Academisch Ziekenhuis Groningen, Groningen, Postbus 30.001, 9700 RB Groningen, Netherlands), Herroelen L, De Klippel N—J Neurol Sci. 1997;145:93-96.
Aspirin reduces the occurrence of ischemic strokes. In some prophylactic trials it was suggested that aspirin might also lessen stroke severity, and hence improve outcome in patients sustaining an ischemic stroke. We examined stroke severity (by using the Mathew scale) and early outcome (Barthel index and mortality on day 21) in 91 patients with an acute (<24 h) ischemic stroke in the territory of the middle cerebral artery. Twenty-seven patients were taking low-dose aspirin (100 or 200 mg/day) prior to their stroke, and 64 were not using antiplatelet drugs. There were no significant differences in baseline stroke severity, early (21 days) mortality or early disability between the two groups. The results of this small study suggest that the use of low-dose aspirin prior to an ischemic stroke does not influence the severity of that stroke and early outcome.
Key Words: cerebral ischemia, aspirin
Magnetic Resonance Imaging of Obliterated Arteriovenous Malformations up to 23 Years After Radiosurgery—Kihlström L (Dept of Neurosurgery, Karolinska Hospital, S-104 01 Stockholm, Sweden), Guo W-Y, Karlsson B, Lindquist C, Lindqvist M—J Neurosurg. 1997;86:589-593.
The authors report outcomes in 18 patients with arteriovenous malformations (AVMs) who were treated with gamma knife radiosurgery and in whom magnetic resonance (MR) imaging was obtained a mean of 14 years (range 8–23 years) after treatment and 10 years (range 4–17 years) after confirmed obliteration of the AVM. All patients were asymptomatic after radiosurgery and during the time of the study. In five patients (28%), cyst formation was observed that corresponded to the site of the obliterated AVM. Cyst formation and contrast enhancement on MR imaging could not be statistically correlated to the radiation dose. In 11 (61%) of the 18 patients, contrast enhancement that was not related to a recanalization of the nidus was observed in the target area. In three patients (17%), an increased T2-weighted signal was detected at the site of previous AVM; this was interpreted as gliosis or demyelination, which appeared to be dose dependent. The study illustrates that cyst formation, contrast enhancement, and an increased T2-weighted signal can be observed in asymptomatic patients in the area that was targeted for AVM radiosurgery up to 23 years after the procedure. The report provides new and essential information about long-term effects on normal tissue after radiosurgery and provides a basis for the interpretation of MR studies in the follow up of small AVMs treated by radiosurgery.
Key Words: cerebral arteriovenous malformations, radiosurgery
Clinical Experience With Epidural Cooling for Spinal Cord Protection During Thoracic and Thoracoabdominal Aneurysm Repair—Cambria RP (Massachusetts General Hospital, 15 Parkman St, WACC 458, Boston, MA 02214), Davison JK, Zannetti S, L’Italien G, Brewster DC, Gertler JP, Moncure AC, LaMuraglia GM, Abbott WM—J Vasc Surg. 1997;25:234-243.
Purpose: This report summarizes our experience with epidural cooling (EC) to achieve regional spinal cord hypothermia and thereby decrease the risk of spinal cord ischemic injury during the course of descending thoracic aneurysm (TA) and thoracoabdominal aneurysm (TAA) repair.
Methods: During the interval July 1993 to Dec. 1995, 70 patients underwent TA (n=9, 13%) or TAA (n=61) (type I, 24 [34%], type II, 11 [15%], type III, 26 [37%]) repair using the EC technique. The latter was accomplished by continuous infusion of normal saline (4°C) into a T11-12 epidural catheter; an intrathecal catheter was placed at the L3-4 level for monitoring of cerebrospinal fluid temperature (CSFT) and pressure (CSFP). All operations (one exception, atriofemoral bypass) were performed with the clamp-and-sew technique, and 50% of patients had preservation of intercostal vessels at proximal or distal anastomoses (30%) or by separate inclusion button (20%). Neurologic outcome was compared with a published predictive model for the incidence of neurologic deficits after TAA repair and with a matched (Type IV excluded) consecutive, control group (n=55) who underwent TAA repair in the period 1990 to 1993 before use of EC.
Results: EC was successful in all patients, with a 1442±718 ml mean (range, 200 to 3500 ml) volume of infusate; CSFT was reduced to a mean of 24°±3°C during aortic cross-clamping with maintenance of core temperature of 34°±0.8°C. Mean CSFP increased from baseline values of 13±8 mm Hg to 31±6 mm Hg during cross-clamp. Seven patients (10%) died within 60 days of surgery, but all survived long enough for evaluation of neurologic deficits. The EC group and control group were well-matched with respect to mean age, incidence of acute presentations/aortic dissection/aneurysm rupture, TAA type distribution, and aortic cross-clamp times. Two lower extremity neurologic deficits (2.9%) were observed in the EC patients and 13 (23%) in the control group (p<0.0001). Observed and predicted deficits in the EC patients were 2.9% and 20.0% (p=0.001), and for the control group 23% and 17.8% (p=0.48). In considering EC and control patients (n=115), variables associated with postoperative neurologic deficit were prolonged (>60 min) visceral aortic cross-clamp time (relative risk, 4.4; 95% CI, 1.2 to 16.5; p=0.02) and lack of epidural cooling (relative risk, 9.8; 95% CI, 2 to 48; p=0.005).
Conclusion: EC is a safe and effective technique to increase the ischemic tolerance of the spinal cord during TA or TAA repair. When used in conjunction with a clamp-and-sew technique and a strategy of selective intercostal reanastomosis, EC has significantly reduced the incidence of neurologic deficits after TAA repair.
Key Words: aneurysm, hypothermia
Items of Interest
Atheromatous Disease of the Thoracic Aorta: Pathologic and Clinical Implications—Kronzon I, Tunick PA (Non-Invasive Cardiology Laboratory, New York University Medical Center, 560 First Ave, New York, NY 10016)—Ann Intern Med. 1997;126:629-637.
Injury Mechanisms in the Ischaemic Penumbra—Approaches to Neuroprotection in Acute Ischaemic Stroke—Ginsberg MD (Cerebral Vascular Disease Research Centre, Dept of Neurology D4-5, University of Miami School of Medicine, 1501 NW 9th Ave, Miami, FL 33136)—Cerebrovasc Dis. 1997;7:7-12.
Neuroprotectants in Late Clinical Development—A Status Report—Wahlgren NG (Dept of Neurology, Karolinska Hospital, S-171 76 Stockholm, Sweden)—Cerebrovasc Dis. 1997;7:13-17.
The Burden of Stroke and Its Sequelae—Gillum RF (Centers for Disease Control and Prevention, Office of Analysis, Epidemiology and Health Promotion, National Center for Health Statistics, 6525 Belcrest Rd, Hyattsville, MD 20782), Wilson JB—Dis Manage Health Outcomes. 1997;1:84-94.
The abstracts in this section have been typeset for consistency with journal format but otherwise appear as in the original articles.
- Copyright © 1997 by American Heart Association