Abstracts of Literature
Mild Hypothermia as a Protective Therapy During Intracranial Aneurysm Surgery: A Randomized Prospective Pilot Trial— Hindman BJ, Todd MM (Dept of Anesthesia, Univ of Iowa, Iowa City, IA 52242), Gelb AW, Loftus CM, Craen RA, Schubert A, Mahla ME, Torner JC—Neurosurgery. 1999;44:23–33.
OBJECTIVE: To conduct a pilot trial of mild intraoperative hypothermia during cerebral aneurysm surgery.
METHODS: One hundred fourteen patients undergoing cerebral aneurysm clipping with (n=52) (World Federation of Neurological Surgeons score ≤III) and without (n=62) acute aneurysmal subarachnoid hemorrhage (SAH) were randomized to normothermic (target esophageal temperature at clip application of 36.5°C) and hypothermic (target temperature of 33.5°C) groups. Neurological status was prospectively evaluated before surgery, 24 and 72 hours postoperatively (National Institutes of Health Stroke Scale), and 3 to 6 months after surgery (Glasgow Outcome Scale). Secondary outcomes included postoperative critical care requirements, respiratory and cardiovascular complications, duration of hospitalization, and discharge disposition.
RESULTS: Seven hypothermic patients (12%) could not be cooled to within 1°C of target temperature; three of the seven were obese. Patients randomized to the hypothermic group more frequently required intubation and rewarming for the first 2 hours after surgery. Although not achieving statistical significance, patients with SAH randomized to the hypothermic group, when compared with patients in the normothermic group, had the following: 1) a lower frequency of neurological deterioration at 24 and 72 hours after surgery (21 versus 37–41%), 2) a greater frequency of discharge to home (75 versus 57%), and 3) a greater incidence of a good long-term outcome (71 versus 57%). For patients without acute SAH, there were no outcome differences between the temperature groups. There was no suggestion that hypothermia was associated with excess morbidity or mortality.
CONCLUSION: Mild hypothermia during cerebral aneurysm surgery is feasible in nonobese patients and is well tolerated. Our results indicate that a multicenter trial enrolling 300 to 900 patients with acute aneurysmal SAH will be required to demonstrate a statistically significant benefit with mild intraoperative hypothermia.
Key Words: subarachnoid hemorrhage, hypothermia
Prospective Blinded Study of the Relationship Between Plasma Homocysteine and Progression of Symptomatic Peripheral Arterial Disease—Taylor LM (Div of Vascular Surgery, OP-11, Oregon Health Sciences Univ, 3181 SW Sam Jackson Park Rd, Portland, OR 97201), Moneta GL, Sexton GJ, Schuff RA, Porter JM, and the Homocysteine and Progression of Atherosclerosis Study Investigators—J Vasc Surg. 1999;29;8–21. Copyright © 1999 by The Society for Cardiovascular Surgery, North American Chapter.
Purpose: An elevated plasma homocysteine level is an established risk factor for atherosclerotic coronary heart disease (CHD), cerebrovascular disease (CVD), and lower extremity occlusive disease (LED). An elevated plasma homocysteine level can be reduced by therapy with folate and vitamins B6 and B12. An accurate evaluation of the role of vitamin therapy requires knowledge of the influence of plasma homocysteine levels on the progression of CHD, CVD, and LED.
Methods: The Homocysteine and Progression of Atherosclerosis Study is a blinded prospective study of the influence of homocysteine and of other atherosclerotic risk factors on the progression of disease in patients with symptomatic CVD, LED, or both. This study is set in a university hospital vascular surgery clinic and the General Clinical Research Center. Consecutive patients with stable symptomatic CVD or LED underwent baseline clinical, laboratory, and vascular laboratory testing for homocysteine and other risk factors and were examined every 6 months. The primary endpoints were ankle brachial pressure index, duplex scan–determined carotid stenosis, and death. The secondary endpoints were the clinical progressions of CHD, LED, and CVD. The hypothesis that was tested was whether the progression of symptomatic CVD or LED was more frequent or more rapid in patients with elevated plasma homocysteine levels.
Results: After a mean follow-up period of 37 months (range, 1 to 78 months) for deaths from all causes (>14 μmol/L; elevated, 18.6%; normal, 9.4%; P=.022), deaths from cardiovascular disease (elevated, 12.5%; normal, 6.3%; P=.05) and the clinical progression of CHD (highest 20% of homocysteine levels, 80%; lowest 20% of homocysteine levels, 39%; P=.007) were significantly more frequent or more rapid by life-table analysis when the homocysteine levels were elevated. Multivariate Cox proportional hazards regression model showed a significant independent and increasing relationship between the plasma homocysteine levels and the time to death (relative risk for highest one third of homocysteine values, 1.6; 95% confidence interval [CI], 1.04 to 2.56; P=0.29; and relative risk for highest one fifth of homocysteine values, 3.13; 95% CI, 1.69 to 6.64; P=0.0001). After an adjustment for age, smoking, hypertension, diabetes, cholesterol, and the vascular laboratory progression of CVD or LED, each 1.0 μmol/L increase in the plasma homocysteine levels resulted in a 3.6% increase (95% CI, 0.0% to 6.6%; P=.06) in the risk of death (all causes) at 3 years and a 5.6% increase (95% CI, 2.2% to 8.5%; P=.003) in the risk of death from cardiovascular disease.
Conclusion: We conclude that elevated plasma homocysteine levels are associated significantly with death, with death from cardiovascular disease, and with the progression of CHD in patients with symptomatic CVD or LED. These results strongly mandate clinical trials of homocysteine-lowering vitamin therapy in such patients.
Key Words: epidemiology, atherosclerosis
Acute Blood Glucose Level and Outcome From Ischemic Stroke—Bruno A (Dept of Neurology, Indiana Univ School of Medicine, 541 Clinical Drive, Rm 365, Indianapolis, IN 46202-5111), Biller J, Adams HP Jr, Clarke WR, Woolson RF, Williams LS, Hansen, MS, for the Trial of ORG 10172 in Acute Stroke Treatment (TOAST Investigators)—Neurology. 1999;52:280–284. Copyright © 1999 by the American Academy of Neurology.
Objective: To study the relation between acute blood glucose level and outcome from ischemic stroke. Background: Hyperglycemia may augment acute ischemic brain injury and increase the risk of hemorrhagic transformation of the infarct. Methods: The authors analyzed the relation between admission blood glucose level (within 24 hours from ischemic stroke onset) and clinical outcome in 1,259 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST)—a placebo-controlled, randomized, double-blind trial to test the efficacy of a low-molecular weight heparinoid in acute ischemic stroke. Very favorable outcome was defined as a Glasgow Outcome Scale score of 1 and a modified Barthel index of 19 or 20. Neurologic improvement at 3 months was defined as a decrease by ≥4 points on the NIH Stroke Scale compared with baseline or a final score of 0. Hemorrhagic transformation of infarct was assessed within 10 days after onset of stroke with repeat cerebral CT. Stroke subtype as lacunar or nonlacunar (atherothromboembolic, cardioembolic, and other or undetermined etiology) was classified by one investigator after completion of stroke evaluation according to study protocol. Results: In all strokes combined (p=0.03) and in nonlacunar strokes (p=0.02), higher admission blood glucose levels were associated with worse outcome at 3 months according to multivariate logistic regression analysis adjusted for stroke severity, diabetes mellitus, and other vascular risks. In lacunar strokes, the relationship between acute blood glucose level and outcome was related to treatment. In the placebo group, higher admission blood glucose levels were associated with better outcome at 3 months. However, in the active drug group, as the glucose level increased from 50 to 150 mg/dL, the probability of a very favorable outcome decreased sharply and remained relatively unchanged as the glucose level increase further (p=0.002, for overall effect of glucose on outcome). Acute blood glucose level was not associated with symptomatic hemorrhagic transformation of infarcts or with neurologic improvement at 3 months. Conclusions: During acute ischemic stroke hyperglycemia may worsen the clinical outcome in nonlacunar stroke, but not in lacunar stroke, and is not associated with an increased risk of hemorrhagic transformation of the infarct.
Key Words: hyperglycemia, cerebrovascular disorders
The Effects of Mannitol on Cerebral Edema After Large Hemispheric Cerebral Infarct—Manno EM, Adams RE, Derdeyn CP, Powers WJ, Diringer MN (Dept of Neurology, Campus Box 8111, 660 S Euclid Ave, St Louis, MO 63110)—Neurology. 1999;52:583–587. Copyright © 1999 by the American Academy of Neurology.
Objective: To evaluate the effect of a single large dose of mannitol on midline tissue shifts after a large cerebral infarction. Background: Theoretically, mannitol use in the largest cerebral infarctions may preferentially shrink noninfarcted cerebral tissue, thereby aggravating midline tissue shifts and worsening neurologic status. To test this theory, we studied patients with hemispheric infarctions using continuous and sequential MRI during administration of a single dose of mannitol. Methods: Patients with neurologic deterioration from complete middle cerebral artery (MCA) infarctions and CT evidence of at least 3 mm of midline shift were studied using T1-weighted three-dimensional multiplanar rapid acquisition gradient echo image data sets acquired at 5- to 10-minute intervals before, during, and after a 1.5 gm/kg bolus infusion of mannitol. Horizontal and vertical displacements were calculated by previously described methods. Glasgow Coma Scale (GCS) and MCA Stroke Scale (MCASS) were measured before and after mannitol administration. Mean changes in tissue shifts were compared using repeated measures analysis of variance. Clinical variables were compared using paired t-tests. Results: Seven patients were enrolled. The final average change in midline shift compared with the initial displacement was 0.0±1 mm for horizontal (F=0.06, p=0.99) and 0.25±1.3 mm for vertical displacement (F=0.06, p=0.99). Whereas average scores for the group did not change, MCASS improved in two, GCS improved in three, and pupillary light reactivity returned in two patients. No patient worsened. Conclusions: Acute mannitol used in patients with cerebral edema after a large hemispheric infarction does not alter midline tissue shifts or worsen neurologic status.
Key Words: cerebrovascular disorders, cerebral edema
Homocysteine and Short-Term Risk of Myocardial Infarction and Stroke in the Elderly—Bots ML, Launer LJ, Lindemans J, Hoes AW, Hofman A, Witteman JCM, Koudstaal PJ, Grobbee DE (Dept of Epidemiologie and Gezundheidsturg, Rijksuniversiteit Utrecht, PO Box 80035, 3508 TA Utrecht, Netherlands)—Arch Intern Med. 1999;159:38–44.
Background: Elevated homocysteine level increases vascular disease risk. Most data are based on subjects younger than 60 years: data for the elderly are more limited. We examined the relationship of homocysteine level to incident myocardial infarction and stroke among older subjects in a nested case-control study.
Methods: Subjects were participants in the Rotterdam Study, a cohort study among 7983 subjects residing in the Ommoord district of Rotterdam, the Netherlands. Baseline examinations were performed from March 1, 1990, to July 31, 1993. The analysis is restricted to myocardial infarction and stroke that occurred before December 31, 1994. One hundred four patients with a myocardial infarction and 120 with a stroke were identified with complete data. Control subjects consisted of a sample of 533 subjects drawn from the study base, free of myocardial infarction and stroke. Nonfasting total homocysteine levels were measured.
Results: Results were adjusted for age and sex. The risk of stroke and myocardial infarction increased directly with total homocysteine. The linear coefficient suggested a risk increase by 6% to 7% for every 1-μmol/L increase in total homocysteine. The risk by quintiles of total homocysteine level was significantly increased only in the group with levels above 18.6 μmol/L (upper quintile): odds ratios were 2.43 (95% confidence interval, 1.11–5.35) for myocardial infarction and 2.53 (95% confidence interval, 1.19–5.35) for stroke. Associations were more pronounced among those with hypertension.
Conclusions: The present study, based on a relatively short follow-up period, provides evidence that among elderly subjects an elevated homocysteine level is associated with an increased risk of cardiovascular disease.
Key Words: cerebrovascular disease, atherosclerosis
Prospective Study of Herpes Simplex Virus, Cytomegalovirus, and the Risk of Future Myocardial Infarction and Stroke—Ridker PM (Brigham and Women’s Hospital, 900 Commonwealth Ave E, Boston, MA 02115), Hennekens CH, Stampfer MJ, Wang F—Circulation. 1998;98:2796–2799. Copyright © 1998 American Heart Association.
Background—It has been hypothesized that infection with either herpes simplex virus (HSV) or cytomegalovirus (CMV) is associated with atherogenesis. However, prospective data relating evidence of prior exposure to these agents with risks of future myocardial infarction (MI) and stroke are sparse.
Methods and Results—In a prospective, nested case-control study of apparently healthy men, the baseline prevalence of antibodies directed against HSV or CMV was similar among 643 men who subsequently developed a first MI or thromboembolic stroke and among 643 age- and smoking-matched men who remained free of reported vascular disease over a 12-year follow-up period. Specifically, the relative risks for future MI and stroke were 0.94 (95% CI, 0.7 to 1.2) for HSV seropositivity and 0.72 (95% CI, 0.6 to 0.9) for CMV seropositivity, after adjustment for other cardiovascular risk factors. These findings were not materially altered in comparisons of early versus late events or in analyses stratified by smoking status. There was no evidence of association between HSV or CMV antibodies and plasma concentration of C-reactive protein, a marker of inflammation that predicts vascular risk in this cohort.
Conclusions—Among apparently healthy middle-aged men. IgG antibodies directed against HSV or CMV do not appear to be a marker for increased atherothrombotic risk. The observed possible inverse relationship of CMV with MI and stroke was unexpected and may well be due to chance, because the direction of association is not compatible with the a priori hypothesis based on proposed biological mechanisms or previous cross-sectional and retrospective data.
Key Words: atherosclerosis, infection
Social Readjustment and Ischemic Stroke: Lack of an Association in a Multiethnic Population—Abel GA, Chen X, Boden-Albala B, Sacco RL (The Neurological Institute, 710 W 168th St, Rm 547, New York, NY 10032)—Neuroepidemiology. 1999;18:22–31. Copyright © 1999 S. Karger AG, Basel.
Clinical experience has suggested that stressful life events and ongoing stressful illness, collectively termed ‘social readjustment’, may precipitate stroke. We investigated the association between a simple in-office evaluation of such stressors and stroke in an urban, multiethnic study population. Cases were patients from the Northern Manhattan Stroke Study with first ischemic stroke; controls were derived through random digit dialing with n:m matching for age, gender, and race-ethnicity. Social readjustment was measured through in-person interview using Amster and Krauss’ Geriatric Social Readjustment Rating Scale (GSRRS), a one-time, 35-item, checklist type weighted questionnaire of stressful life events occurring in the previous 6 months. Conditional logistic regression was used to analyze the GSRRS and its quartiles as well as stressful events subgroups, adjusting for education, hypertension, cardiac disease, diabetes, and number of weekly visits as a measure of socialization. Six hundred and fifty-five cases of ischemic stroke and 1,087 controls were utilized. The mean age of the cases was 69.8 years, with 55.4% women, 51.0% Hispanics, 28.4% blacks, and 19.1% whites. GSRRS scores ranged from 0 to 812; the mean score was 205.5 for the cases and 206.2 for the controls. The analysis showed no association between stroke and a 20-point increase on the GSRRS (OR=1.01, 95% CI=0.99–1.01). There was also no effect for the second, third or highest versus lowest quartile. No association was found in age, gender or race-ethnic subgroups, or when analyzing negative events, severely threatening events, or ongoing stressful illnesses separately. While this study does not preclude social readjustment as a stroke risk factor, it suggests that the one-time assessment often done in the medical office setting has little relevance for stroke prevention planning.
Key Words: stress, psychological, epidemiology
Neuroprotective Effects of the Novel Glutamate AMPA Receptor Antagonist YM872 Assessed with in Vivo MR Imaging of Rat MCA Occlusion—Håberg A, Takahashi M, Yamaguchi T, Hjelstuen M, Haraldseth O (MR-Center Univ Hospital, RIT, N-7006 Trondheim, Norway)—Brain Res. 1998;811:63–70. Copyright © 1998 Elsevier Science.
The neuroprotective effect of post-ischemic treatment with the novel, highly water-soluble, glutamate AMPA receptor antagonist YM872 was evaluated by using MR imaging and histopathology of rats subjected to permanent MCA occlusion. Two treatment groups with continuous i.v. infusion of 20 mg kg−1 h−1 YM872 during either the first 4 h or first 24 h after MCA occlusion, called 4 h YM872 treatment group (n=9) and 24 h YM872 treatment group (n=8) respectively, were compared to a control group (n=8). The main end-point was T2 weighted MR imaging and histopathology 24 h after MCA occlusion. Also the time evolution of the ischemic tissue damage was studied by diffusion weighted MR imaging 4 and 24 h after MCA occlusion. The volume of ischemic tissue damage as assessed by diffusion weighted MR imaging 41/2 h after MCA occlusion was significantly smaller in both YM872 treatment groups (99±52 mm3 and 102±44 mm3 compared to 186±72 mm3 in the control group, ±S.D. and p=0.008). The infarct volume as assessed by T2 weighted MR imaging 24 h after MCA occlusion was significantly smaller only in the 24 h YM872 treatment group (262±57 mm3 compared to 366±49 mm3 in the control group, ±S.D. and p=0.01) while the infarct volume in the 4 h YM872 treatment group (357±88 mm3) was similar to the control group. YM872 treatment significantly reduced the infarct volume 24 h after MCA occlusion when the drug was administered as continuous infusion during the 24-h observation period.
Key Words: cerebral ischemia, stroke, experimental
Glutamate Receptor Antagonists Inhibit Calpain-Mediated Cytoskeletal Proteolysis in Focal Cerebral Ischemia—Minger SL, Geddes JW, Holtz ML, Craddock SD, Whiteheart SW, Siman RG, Pettigrew LC (The Stroke Program of the Sanders-Brown Center on Aging, 101 Sanders-Brown Building, Univ of Kentucky College of Medicine, 800 S Limestone St, Lexington, KY 40536-0230)—Brain Res. 1998;810:181–199. Copyright © 1998 Elsevier Science B.V.
Excitatory amino acids may promote microtubular proteolysis observed in ischemic neuronal degeneration by calcium-mediated activation of calpain, a neutral protease. We tested this hypothesis in an animal model of focal cerebral ischemia without reperfusion. Spontaneously hypertensive rats were treated with 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo-(F)quinoxaline (NBQX), a competitive antagonist of the neuronal receptor for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), or cis-4-[phosphono-methyl]-2-piperidine carboxylic acid (CGS 19755), a competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor. After treatment, all animals were subjected to permanent occlusion of the middle cerebral artery for 6 or 24 h. Infarct volumes measured in animals pretreated with CGS 19755 after 24 h of ischemia were significantly smaller than those quantified in ischemic controls. Rats pretreated with NBQX showed partial amelioration of cytoskeletal injury with preserved immunolabeling of microtubule-associated protein 2 (MAP 2) at 6 and 24 h and reduced accumulation of calpain-cleaved spectrin byproducts only at 6 h. Prevention of cytoskeletal damage was more effective after pretreatment with CGS 19755, as shown by retention of MAP 2 immunolabeling and significant restriction of calpain activity at both 6 and 24 h. Preserved immunolabeling of tau protein was observed at 6 and 24 h only in animals pretreated with CGS 19755. Western analysis performed on ischemic cortex taken from controls or rats pretreated with either NBQX or CGS 19755 suggested that loss of tau protein immunoreactivity was caused by dephosphorylation, rather than proteolysis. These results demonstrate a crucial link between excitotoxic neurotransmission, microtubular proteolysis, and neuronal degeneration in focal cerebral ischemia.
Key Words: nerve degeneration, microtubule-associated proteins
Estrogen Attenuates Over-Expression of β-Amyloid Precursor Protein Messager RNA in an Animal Model of Focal Ischemia—Shi J, Panickar KS, Yang SH, Rabbani O, Day AL, Simpkins JW (PO Box 100487, JHMHC, College of Pharmacy, Univ of Florida, Gainesville, FL 32610)—Brain Res. 1998;810:87–92. Copyright © 1998 Elsevier Science B.V.
Cerebral ischemia is a risk factor for late onset Alzheimer’s disease. Since estrogen replacement therapy benefits the outcome of cerebral stroke in post-menopausal women, we designed the present study to investigate the effects of estrogen on the expression of β-amyloid precursor protein (APP) mRNA following focal ischemia in female rats. Female rats were ovariectomized (OVX) for two weeks. A single dose of 17 β-estradiol (E2) (100 μg/kg) was injected s.c. two hours before a unilateral middle cerebral artery (MCA) occlusion. Brain samples were harvested from ischemic core and penumbra of cortices at one hour and twenty-four hours following MCA occlusion. The expression of APP mRNA was assessed by RT-PCR. At one hour after MCA occlusion, OVX rats had a 67.9% (p<0.05) increase in APP mRNA in the penumbra. E2 treatment reduced this APP mRNA over-expression by 26.3% at that region. At twenty four hours following MCA occlusion, OVX rats had increases in APP mRNA of 52.9% and 57.0% (p<0.05) in the core and penumbra, respectively. E2 treatment reduced the APP mRNA over-expression by 61.0% and 48.6% (p<0.05) in these two regions, respectively. These effects appeared to reflect an interaction between hormonal environment and ischemia, since in the absence of MCA occlusion, there were no significant differences in APP mRNA expression among OVX, OVX-E2 treated and intact female rats. The present study demonstrates that estrogen may have an important role in reducing the over-expression of APP mRNA following focal ischemia.
Key Words: middle cerebral atery, cerebral blood flow
Increased Therapeutic Efficacy with rt-PA and Anti-CD18 Antibody Treatment of Stroke in the Rat—Zhang RL, Zhang ZG, Chopp M (Henry Ford Hospital, Neurology Dept, 2799 W Grand Blvd, Detroit, MI 48202)—Neurology. 1999;52:273–279. Copyright © by the American Academy of Neurology.
Objective: To examine the efficacy of an antileukocyte adhesion antibody (anti-CD18) as an adjuvant for delayed (2 hours and 4 hours) thrombolytic therapy (recombinant human tissue plasminogen activator [rt-PA]) in middle cerebral artery occlusion (MCAO) in rats. Background: Thrombolytic therapy with rt-PA is limited in its application by a short therapeutic window. Methods: Male Wistar rats were subjected to MCAO by a single fibrin-rich clot. The rats were assigned to the following experimental groups: Experiment 1 (treatment 2 hours after embolization), 1) rt-PA, 2) anti-CD18 antibody, 3) rt-PA and anti-CD18 antibody, 4) immunoglobulin (Ig) G, and 5) vehicle; Experiment 2 (treatment 4 hours after occlusion), 1) rt-PA alone, 2) rt-PA and anti-CD18 antibody, and 3) nontreated control group. Neurologic deficits, infarction volume, hemorrhage, and brain myeloperoxidase (MPO) immunoreactivity were measured. Results: Administration of rt-PA and anti-CD18 antibody 2 hours later reduced significantly (p<0.05) the infarct volume and improved neurologic deficits compared with the vehicle-treated group. Treatment with rt-PA alone improved neurologic deficits significantly and reduced mean infarct volume compared with the vehicle-treated group. However, treatment with anti-CD18 antibody neither reduced infarct volume nor improved neurologic deficits compared with the IgG-treated group. The combination of rt-PA and anti-CD18 antibody treatment at 4 hours reduced significantly the infarct volume and MPO immunoreactive cells compared with rt-PA treatment alone at 4 hours, and reduced neurologic deficits compared with rt-PA treatment alone and compared with the nontreated animals. Conclusions: The combination of antileukocyte adhesion antibody and thrombolytic therapy may increase the therapeutic window for the treatment of stroke.
Key Words: middle cerebral artery, stroke, experimental
No Evidence for an Ischemic Penumbra in Massive Experimental Intracerebral Hemorrhage—Qureshi AI, Wilson DA, Hanley DF, Traystman RJ (Dept of Anesthesiology/Critical Care Medicine, Blalock 1408, 600 N Wolfe St, Baltimore, MD 21287)—Neurology. 1999;52:266–272. Copyright © by the American Academy of Neurology.
Objectives: To determine the effect of massive intracerebral hemorrhage (ICH) on regional cerebral blood flow (rCBF) and metabolism, and to test the hypothesis that there is persistent ischemia in the perihematoma region after ICH. Background: Cerebral ischemia is postulated to be one of the mechanisms of neural injury after ICH. Presumably the hematoma induces ischemia by mechanical compression of the surrounding microvasculature. Methods: The authors induced ICH in eight anesthetized mongrel dogs by autologous blood injection (7.5 mL) under arterial pressure in the deep white matter adjacent to the left basal ganglia. They measured serial rCBF using radiolabeled microspheres in regions around and distant to the hematoma, as well as cerebral oxygen extraction, oxygen consumption (CMRO2), glucose utilization, and lactate production by serial sampling of cerebral venous blood from the sagittal sinus. Mean arterial pressure (MAP) and intracranial pressure (ICP) were monitored continuously. All measurements were recorded at 0.5, 1.0, 2.0, 3.5, and 5.0 hours after induction of ICH and compared with prehematoma values. Evans Blue dye was injected at the end of the experiment, and intensity of staining was compared with three control animals. Results: Compared with prehematoma ICP (12.5±2.0 mm Hg, mean±standard error), significant elevation in ICP was observed after ICH peaking at 5 hours (34.4±5.2 mm Hg). Compared with prehematoma MAP (125.8±7.0 mm Hg), significant elevation in MAP was observed at 120 minutes after onset of hematoma (139.1±4.6 mm Hg), with return to the prehematoma value by 5 hours. There were no significant changes observed in cerebral oxygen extraction (51.4±4.3% versus 44.8±4.9%) and CMRO2 (1.8±0.3 versus 1.64±0.2 mL O2/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. There were no significant differences observed in rCBF in the perihematoma gray (18.2±0.9 mL/100 g/min versus 20.1±1.5 mL/100 g/min) or white matter (15.6±1.4 mL/100 g/min versus 15.3±1.1 mL/100 g/min) at 5 hours posthematoma (or any other posthematoma measurement) compared with prehematoma values. No changes were observed in cerebral glucose utilization, lactate production, and rCBF in other regions after introduction of ICH. Permeability of the blood–brain barrier was more prominent in the ipsilateral hemisphere in animals with ICH compared with control animals. Conclusions: Despite a prominent increase in ICP and MAP after ICH, the authors found no evidence to support the presence of an ischemic penumbra in the first 5 hours after ICH. Thus, other mechanisms for acute neural injury and late rCBF changes after ICH must be investigated.
Key Words: cerebral blood flow, stroke, experimental
Cerebral Vasomotor Reactivity and Cerebral White Matter Lesions in the Elderly—Bakker SLM (Dept of Neurology, Univ Hospital Rotterdam, Dr Molewaterplein 40, 3015 GD Rotterdam, Netherlands), de Leeuw F-E, de Groot JC, Hofman A, Koudstaal PJ, Breteler MMB—Neurology. 1999;52:578–583. Copyright © 1999 by the American Academy of Neurology.
Objective: The pathogenesis of white matter lesions is still uncertain, but an ischemic-hypoxic cause has been suggested. Cerebral vasomotor reactivity reflects the compensatory dilatory mechanism of the intracerebral arterioles to a vasodilatory stimulus and provides a more sensitive hemodynamic index than the level of resting flow. Methods: The authors determined the association between vasomotor reactivity and white matter lesions in 73 consecutive individuals from the Rotterdam Scan Study who also participated in the Rotterdam Study, a large population-based prospective follow-up study of individuals ≥55 years old. Vasomotor reactivity was measured by means of CO2-enhanced transcranial Doppler, and in all individuals axial T1*-, T2*-, and proton density (PD)-weighted MRI scans (1.5 T) were obtained. White matter lesions were scored according to location, size, and number by two independent readers. Results: Vasomotor reactivity was inversely associated with the deep subcortical and total periventricular white matter lesions (OR 0.5, 95% CI 0.3 to 1.1; and OR 0.7, 95% CI 0.4 to 1.1, respectively). A strong association was found between impaired vasomotor reactivity and periventricular white matter lesions adjacent to the lateral ventricular wall (OR 0.6, 95% CI 0.4 to 1.0; p=0.001). No association was found with periventricular white matter lesions near the frontal and occipital horns. Conclusions: Our data confirm the association between vasomotor reactivity and white matter lesions and support the hypothesis that some white matter lesions may be associated with hemodynamic ischemic injury to the brain.
Key Words: aging, vasomotor reactivity
Diffusion-Weighted MR Imaging: Diagnostic Accuracy in Patients Imaged Within 6 Hours of Stroke Symptom Onset—González, RG (Div of Neuroradiology and Stroke Service, Massachusetts General Hospital and Harvard Medical School, GRB 285, Fruit St, Boston, MA 02114-2696), Schaefer PW, Buonanno FS, Schwamm LH, Budzik RF, Rordorf G, Wang B, Sorensen AG, Koroshetz WJ—Radiology. 1999;210:155–162.
PURPOSE: To evaluate the diagnostic accuracy of diffusion-weighted magnetic resonance (MR) imaging performed within 6 hours of the onset of stroke symptoms.
MATERIALS AND METHODS: The authors reviewed the patient records and images from all patients hospitalized in a 10-month period in whom diffusion-weighted imaging was performed within 6 hours of the onset of strokelike symptoms (n=22). Analyses included comparison of the initial interpretation of the diffusion-weighted images with the final clinical diagnosis; blinded reviews of computed tomographic (CT) scans and conventional and diffusion-weighted images; and determination of lesion contrast-to-noise ratios (CNRs).
RESULTS: Diffusion-weighted images indicated stroke in 14 patients, all of whom had a final diagnosis of acute stroke. Diffusion-weighted images were negative in eight patients, all of whom had a final clinical diagnosis other than stroke (100% sensitivity, 100% specificity, χ2=23.00, P<.0001). Blinded reviews yielded 100% sensitivity and 86% specificity for diffusion-weighted MR imaging (χ2=15.43, P<.0005); 18% sensitivity and 100% specificity for conventional MR imaging (χ2=2.85, P>.2); and 45% sensitivity and 100% specificity for CT (χ2=4.40, P>.10). Lesion percentage CNRs were 77% for diffusion-weighted imaging, 5.5% for CT, 9.8% for T2-weighted MR imaging, and 3.1% for proton-density–weighted MR imaging (P<.002 for diffusion-weighted imaging vs others).
CONCLUSION: Diffusion-weighted MR imaging is highly accurate for diagnosing stroke within 6 hours of symptom onset and is superior to CT and conventional MR imaging.
Key words, stroke, acute, magnetic resonance imaging
Cerebral Microemboli During Left Heart Catheterization—Fischer A, Özbek C, Bay W, Hamann GF (Dept of Neurology, Ludwig-Maximilians-Univ Marchioninistr 15, D-81377 Munich, Germany)—Am Heart J. 1999;137:162–168.
Background The aim of this study was to describe the rate of microemboli signals (MES) during left heart catheterization (LHC).
Methods A monitoring of both middle cerebral arteries using transcranial Doppler ultrasonography was performed to investigate cerebral microemboli during LHC. Seventy-two patients undergoing LHC and 29 patients with LHC followed by coronary intervention were studied.
Results During a standardized LHC (n=52), 95±45 MES were detected of which 67.5% occurred during injection of contrast media or saline solution, 30% during movements of wire and catheter, and 2% during catheter manipulation. During coronary interventions only, rotablation (n=2) was followed by a massive increase in MES. The use of injection fluids prepared with minor gas content reduced the MES rate by 67% (P<.05). All MES were clinically silent.
Conclusions Cerebral microembolism is a current finding during LHC. The dependence of the MES rate during diagnostic LHC on the gas content of the injection fluids provides evidence that most of the MES are caused by microbubbles and not by solid emboli. The high rate of MES during coronary rotablation may be explained by the formation of cavitation bubbles. The clinical results of the MES during LHC appear to be benign.
Key Words: cerebral embolism, cardiac catheterization
Pattern and Significance of Cerebral Microemboli During Coronary Artery Bypass Grafting—Sylivris S (Austin and Repartriation Medical Center, Studley Road, Heidelberg 3084, Victoria, Australia) Levi C, Matalanis G, Rosalion A, Buxton BF, Mitchell A, Fitt G, Harberts DB, Saling MM, Tonkin AM—Ann Thorac Surg. 1998;66:1674–1678. Copyright © 1998 by the Society of Thoracic Surgeons.
Background. Strokes that occur during coronary artery bypass grafting are often caused by embolism. Intraoperative transcranial Doppler monitoring can detect cerebral microemboli. The aims of this study were to identify the pattern of microembolic phenomena during various stages of coronary artery bypass grafting, to verify whether numbers of high-intensity transient signals correlated with early neuropsychologic deficits, and to identify, using magnetic resonance imaging scans, whether radiologic evidence of cerebral infarction correlated with microembolic numbers during the bypass period.
Methods. Forty-one consecutive patients undergoing coronary bypass grafting with transcranial Doppler monitoring were enrolled in this study. All had preoperative and postoperative magnetic resonance imaging brain scans. A subgroup of 32 patients were studied by comparing microembolic load and early neuropsychological outcomes.
Results. Transcranial Doppler monitoring confirmed that most microemboli occurred during cardiopulmonary bypass. A significant early neuropsychological deficit after coronary artery bypass grafting did correspond to the total microembolic load during bypass (p=0.008). However, patients with cerebral infarction on magnetic resonance imaging had significantly more microembolic signal during the preincision phases and not during the bypass period.
Conclusions. Microembolic load during bypass is associated with early neuropsychologic deficits. In contrast, patients who show evidence of strokes during coronary artery bypass grafting have a higher microembolic load during the preincision phase than those without cerebral infarction. Differing mechanisms may be responsible for these different outcomes.
Key Words: cerebral embolism, coronary artery disease
Can Simple Clinical Features Be Used to Identify Patients With Severe Carotid Stenosis on Doppler Ultrasound?—Mead GE (Dept of Clinical Neurosciences, Univ of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, UK), Wardlaw JM, Lewis SC, McDowall M, Dennis MS—J Neurol Neurosurg Psychiatry. 1999;66:16–19.
Objectives—Carotid endarterectomy reduces the risk of stroke in symptomatic patients with severe ipsilateral carotid stenosis. Symptomatic patients should therefore undergo carotid Doppler imaging, but in some centres access to imaging is limited. It was therefore investigated whether simple clinical features alone or in combination could be used to identify patients with severe carotid stenosis, so that they could be referred preferentially for carotid imaging.
Methods—1041 patients with acute stroke, cerebral or retinal transient ischaemic attacks, and retinal strokes admitted to Western General Hospital or seen in neurovascular clinics were assessed by a stroke physician. Their carotid arteries were investigated using colour Doppler imaging by a consultant neuroradiologist. Patients with primary intracerebral haemorrhage, total anterior circulation strokes, posterior circulation strokes, or posterior circulation transient ischaemic attacks were excluded because carotid surgery would be inappropriate.
Results—726 patients were used in the analysis. Stepwise logistic regression showed that there were significant positive associations between severe carotid stenosis and an ipsilateral bruit, diabetes mellitus, and previous transient ischaemic attacks; and a negative association with lacunar events. The strategy with the highest specificity (97%) was “any three of these four features” but sensitivity was only 17%. The strategy with the highest sensitivity (99%) was to use one or more of the four features, but specificity was only 22%.
Conclusion—None of the strategies identified all patients with severe carotid stenosis with a reasonable specificity. When access to carotid imaging is severely limited, simple clinical features are of some use in prioritising patients for imaging, but access to carotid imaging should be improved.
Key Words: carotid artery occlusion, ultrasonography
Frequency of Major Complications of Aspirin, Warfarin, and Intravenous Heparin for Secondary Stroke Prevention—Petty GW (Mayo Clinic, 200 First Street SW, Rochester, MN 55905), Brown RD, Whisnant JP, Sicks JD, O’Fallon WM, Wiebers DO—Ann Intern Med. 1999;130:14–22. Copyright © 1999 American College of Physicians-American Society of Internal Medicine.
Background: Complication rates of medical therapy for secondary stroke prevention derived from clinical trials may or may not be applicable to patients with cerebrovascular disease in the general population.
Objective: To determine complication rates for aspirin, warfarin, and intravenous heparin administered for secondary stroke prevention after first episodes of ischemic stroke, transient ischemic attack, or amaurosis fugax in a community.
Design: Population-based historical cohort study.
Setting: Rochester, Minnesota.
Patients: All residents of Rochester who, between 1985 and 1989, received aspirin (n=339) or warfarin (n=145) within 2 years after first ischemic stroke, transient ischemic attack, or amaurosis fugax or received intravenous heparin (n=201) within 2 weeks after first ischemic stroke, transient ischemic attack, or amaurosis fugax.
Measurements: Occurrence of major complications caused by therapy.
Results: Twenty aspirin-associated complications (1 fatal) occurred during an average 1.7 years of treatment, 8 warfarin-associated complications occurred during an average 0.7 years of treatment, and 3 heparin-associated complications (1 fatal) occurred during an average 5.1 days of treatment. Complication rates were 3.5 per 100 person-years (95% CI, 2.1 to 5.4) for aspirin, 7.9 per 100 person-years (CI, 3.4 to 15.6) for warfarin, and 0.30 (CI, 0.06 to 0.86) per 100 person-days for heparin. Rates of fatal complications were 0.2 per 100 person-years (CI, 0 to 1.0) for aspirin, 0 per 100 person-years (CI, 0 to 3.6) for warfarin, and 0.10 per 100 person-days (0 to 0.55) for heparin.
Conclusions: Complication rates for warfarin and intravenous heparin given as therapy for secondary stroke prevention in Rochester, Minnesota, were lower than rates reported from earlier trials and observational studies. However, complication rates for warfarin were higher than in more recent referral-based studies and multicenter randomized trials. After adjustment for duration of therapy, complication rates for heparin were higher than those for aspirin or warfarin. These rates can be used to judge the applicability of complication rates derived from ongoing clinical trials.
Key Words: cerebrovasular disorders, epidemiology
Decreasing Incidence of Stroke During Valvular Surgery—Borger MA, Ivanov J, Weisel RD (Division of Cardiovascular Surgery, Toronto Hospital, EN 14-215, 200 Elizabeth St, Toronto, Ontario, Canada M5G 2C4), Peniston CM, Mickleborough LL, Rambaldini G, Cohen G, Rao V, Feindel CM, David TE—Circulation. 1998;98(suppl II):II-137–II-143. Copyright © 1998 American Heart Association, Inc.
Background—The predictors and causes of stroke after valvular surgery are incompletely defined. We examined the incidence, predictors, and mechanisms of stroke during valvular procedures over a 15-year time period.
Methods and Results—We retrospectively reviewed prospectively gathered data on 5954 consecutive patients undergoing valvular procedures at our institution from 1982 to 1996. Stroke was defined as persistent central nervous system deficit, usually with confirmatory CT imaging. Patients were divided into 3 groups according to date of operation: group 1, 1982 to 1986 (n=1819); group 2, 1987 to 1991 (n=2022); and group 3, 1992 to 1996 (n=2113). Chart review was undertaken of all patients who developed stroke (n=189). Stroke occurred in 3.8% of group 1 patients, 3.3% of group 2, and 2.6% of group 3 (P=0.120). The decreasing incidence of stroke over time was confirmed by multivariable logistic regression analysis, in which earlier date of operation was an independent risk factor for stroke (P<0.001). Predictors of stroke identified by multivariable logistic regression were (listed in decreasing order): (1) endocarditis (OR, 3.0; 95% CI, 1.8 to 5.0); (2) age >74 years (OR, 2.3; 95% CI, 1.5 to 3.7); (3) earlier time period of operation (1982 to 1986: OR, 2.2; 95% CI, 1.5 to 3.2; 1987 to 1991: OR, 1.5; 95% CI, 1.0 to 2.2); (4) urgent timing (OR, 2.0; 95% CI, 1.4 to 2.8); (5) concomitant coronary bypass (OR, 2.0; 95% CI, 1.4 to 2.8); and (6) reoperation (OR, 1.7; 95% CI, 1.2 to 2.4). In more recent years of operation, we found an increasing prevalence of age >74 years (7.4% in group 1, 9.5% in group 2, and 15.3% in group 3; P<0.001), urgent timing (11%, 26%, and 34%; P<0.001), and concomitant coronary bypass surgery (25%, 27%, and 33%; P<0.001).
Conclusions—The incidence of stroke during valvular surgery has decreased with time, despite an increased prevalence of risk factors. Predictors of stroke suggest 3 major causes (multivariable predictors in parentheses): atherosclerotic emboli (elderly age, concomitant coronary bypass), shock (urgent timing, reoperation), and septic emboli (endocarditis).
Key Words: cardioembolic stroke, risk factors
Intracerebral Hemorrhage After Carotid Endarterectomy: Incidence, Contribution to Neurologic Morbidity, and Predictive Factors—Ouriel K (Box 652, Univ of Rochester, 601 Elmwood Ave, Rochester, NY 14642), Shortell CK, Illig KA, Greenberg RK, Green RM—Vasc Surg. 1999;29:82–89. Copyright © 1999 by the Society for Vascular Surgery and International Society for Cardiovascular Surgery, North American Chapter.
Purpose: With a diminishing rate of cardiac and neurologic events after carotid endarterectomy, intracerebral hemorrhage is gaining increasing importance as a cause of perioperative morbidity and mortality. To date, information has been largely anecdotal, and there has been no comparison with a control group of patients.
Methods: The records of all patients experiencing symptomatic intracerebral hemorrhage after carotid endarterectomy were reviewed and compared with data from 50 randomly selected patients who did not experience intracranial bleeding. Univariate analyses were performed, using the Fisher exact test for dichotomous data and the Student t test for continuous data.
Results: During a 6-year period, symptomatic intracranial hemorrhage developed in 11 (0.75%) of 1471 patients undergoing carotid endarterectomy, accounting for 35% of the 31 total perioperative neurologic events. Hemorrhage occurred a median of 3 days postoperatively (range, 0 to 18 days). Signs and symptoms included hypertension in all 11 patients, headache in 7 conscious patients (64%), and bradycardia in 6 patients (55%). Massive hemorrhage with herniation and death occurred in 4 patients (36%). Moderate hemorrhage developed in 5 patients (45%); 3 of these patients had partial recovery, and 2 had complete recovery. Petechial hemorrhage occurred in the remaining 2 patients (18%), 1 with partial and 1 with complete recovery. In comparison with the control group, there were no differences in respect to sex, indication for operation, smoking or diabetic history, and antiplatelet therapy or perioperative heparin management. Patients with intracranial hemorrhage were, however, younger, more frequently hypertensive, had a higher degree of ipsilateral and contralateral carotid stenosis, and had a higher rate of contralateral carotid occlusion.
Conclusion: Intracranial hemorrhage occurs with notable frequency after carotid endarterectomy and accounts for a significant proportion of neurologic morbidity and mortality. Younger patients, hypertensive patients, and patients with severe cerebrovascular occlusive disease appear to be at greatest risk for the complication.
Key Words: cerebrovascular disorders, surgery
Cranial and Cervical Nerve Injuries After Carotid Endarterectomy: A Prospective Study—Ballotta E (Vascular Surgery Section, First Institute of General Surgery, Univ of Padua, School of Medicine, Policlinico Universitario, Via N Giustiniani, 2 35128 Padova, Italy), Da Giau G, Renon L, Narne S, Saladini M, Abbruzzese E, Meneghetti G—Surgery. 1999;125:85–91. Copyright © 1999 by Mosby, Inc.
Background. The purpose of this study was to review the outcome of patients who had cranial and cervical nerve injuries after carotid endarterectomy (CEA).
Methods. This prospective study reviewed 200 consecutive CEAs. Preoperative and postoperative cranial nerve assessment was completed on all patients. Neurologic evaluation included routine direct fiberoptic laryngoscopy. Patients found to have no neurologic injury had no further follow-up. Patients with postoperative peripheral neurologic dysfunction were enrolled for regular long-term follow-up to assess delayed recovery.
Results. Overall, 25 (12.5%) nerve injuries were identified in 24 patients. There were 11 (5.5%) hypoglossal, 8 (4%) recurrent laryngeal, 2 (1%) superior laryngeal, 2 (1%) marginal mandibular, and 2 (1%) greater auricular nerve injuries. None of the patients were lost to follow-up. All nerve dysfunctions were transient, with all but 4 nerves recovering completely within 6 months. The recovery took from 1 week to 37 months, with a mean recovery time of 5.8 months. Two patients with recurrent laryngeal nerve dysfunction were found to have prolonged full recovery time (ie, 31 and 37 months, respectively). Two patients successfully underwent contralateral CEA, although movement of the opposite vocal cord was not fully restored.
Conclusions. Cranial nerve injury after CEA is a common occurrence and can be classified as a “major” or “minor” complication, depending on the severity of the clinical consequences. Extended follow-up will identify the specific subset of patients with a late complete nerve recovery.
Key Words: complications, carotid endarterectomy
Items of Interest
Sexual Dysfunction in Stroke Patients—Korpelainen JT (Dept of Neurology, Univ of Oulu, Kajaanintie 52, FIN-90220 Oulu, Finland), Kauhanen M-L, Kemola H, Malinen U, Myllylä VV—Acta Neurol Scand. 1998;98:400–405, Copyright © Munksgaard 1998.
Low-Molecular-Weight Heparins—Huang, JN (Dana Farber Cancer Institute, 44 Binney St, Boston, MA 02115), Shimamura A—Coagulation Disord. 1998;12:1251–1281.
Swallowing Disorders—Domenech E, Kelly J (Dept of Otolaryngology-Head and Neck Surgery, Greater Baltimore Medical Center, 6701 N Charles Street, Rm 4202, Baltimore, MD 21204)—Swallowing Disord. 1999;83:97–113.
Diabetes Mellitus and Cerebrovascular Disease—Lukovits TG (Dept of Neurological Sciences, Rush–Presbyterian–St Luke’s Medical Center, 1725 W Harrison St, Suite 755, Chicago, IL 60612), Mazzone T, Gorelick PB—Neuroepidemiology. 1999;18:1–14. Copyright © 1999 S. Karger AG, Basel.
Carotid-Artery Intima and Media Thickness as a Risk Factor for Myocardial Infarction and Stroke in Older Adults—O’Leary DH (CHS Coordinating Center, Century Sq, 1501 4th Ave, Suite 2025, Seattle, WA 98101), Polak JF, Kronmal RA, Manolio TA, Burke GL, Wolfson SK—N Engl J Med. 1999;340:14–22. Copyright © 1999, Massachusetts Medical Society.
The abstracts in this section have been typeset for consistency with journal format but otherwise appear as in the original articles.
- Copyright © 1999 by American Heart Association