Carotid endarterectomy--an evidence-based review: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology.

OBJECTIVE: To assess the efficacy of carotid endarterectomy for stroke prevention in asymptomatic and symptomatic patients with internal carotid artery stenosis. Additional clinical scenarios, such as use of endarterectomy combined with cardiac surgery, are also reviewed. METHODS: The authors selected nine important clinical questions. A systematic search was performed for articles from 1990 (the year of the last statement) until 2001. Additional articles from 2002 through 2004 were included using prespecified criteria. Two reviewers also screened for other relevant articles from 2002 to 2004. Case reports, review articles, technical studies, and single surgeon case series were excluded. RESULTS: For several questions, high quality randomized clinical trials had been completed. Carotid endarterectomy reduces the stroke risk compared to medical therapy alone for patients with 70 to 99% symptomatic stenosis (16% absolute risk reduction at 5 years). There is a smaller benefit for patients with 50 to 69% symptomatic stenosis (absolute risk reduction 4.6% at 5 years). There is a small benefit for asymptomatic patients with 60 to 99% stenosis if the perioperative complication rate is low. Aspirin in a dose of 81 to 325 mg per day is preferred vs higher doses (650 to 1,300 mg per day) in patients undergoing endarterectomy. CONCLUSIONS: Evidence supports carotid endarterectomy for severe (70 to 99%) symptomatic stenosis (Level A). Endarterectomy is moderately useful for symptomatic patients with 50 to 69% stenosis (Level B) and not indicated for symptomatic patients with <50% stenosis (Level A). For asymptomatic patients with 60 to 99% stenosis, the benefit/risk ratio is smaller compared to symptomatic patients and individual decisions must be made. Endarterectomy can reduce the future stroke rate if the perioperative stroke/death rate is kept low (<3%) (Level A). Low dose aspirin (81 to 325 mg) is preferred for patients before and after carotid endarterectomy to reduce the rate of stroke, myocardial infarction, and death (Level A).

Single nucleotide polymorphism in CTH associated with variation in plasma homocysteine concentration.

Plasma total homocysteine (tHcy) concentration, an independent risk factor of atherosclerosis, has numerous genetic and environmental determinants. While the thermolabile polymorphism in MTHFR encoding methylenetetrahydrofolate reductase is the best-studied genetic factor associated with variation in plasma tHCy, other candidate genes are being evaluated. Recently, we discovered that cystathioninuria was caused by mutations in the CTH gene encoding cystathionine gamma-lyase, an enzyme that converts cystathionine to cysteine in the trans-sulfuration pathway. We also identified a common single nucleotide polymorphism (SNP), namely c.1364G>T (S403I) in exon 12 of CTH. In the current analysis, we studied the association of genotypes of this SNP with plasma tHcy concentrations in 496 Caucasian subjects. CTH 1364T/T homozygotes had significantly higher mean plasma tHcy concentration than subjects with other genotypes, and the effect sizes of CTH and MTHFR genotypes were similar. The findings suggest that common variation in CTH may be a determinant of plasma tHcy concentrations.

Relationship between blood pressure and stroke risk in patients with symptomatic carotid occlusive disease.

BACKGROUND AND PURPOSE: Blood pressure lowering in patients with a previous transient ischemic attack (TIA) or stroke reduces the risk of recurrent stroke and coronary vascular events. However, there is uncertainty about the risks and benefits in patients with severe carotid occlusive disease, particularly those with a carotid occlusion or bilateral > or =70% carotid stenosis in whom cerebral perfusion is often impaired and may depend directly on systemic blood pressure. Therefore, we studied the effect of carotid artery disease on the relationship between blood pressure and stroke risk in patients with recent TIA or stroke. METHODS: We compared the relationship between blood pressure (systolic and diastolic blood pressures, pulse pressure) and stroke risk in TIA and stroke patients with documented stenosis of at least 1 carotid artery [European Carotid Surgery Trial (ECST) and North American Symptomatic Carotid Endarterectomy Trial (NASCET)] with that in TIA and stroke patients with a low prevalence of carotid disease [United Kingdom Transient Ischaemic Attack (UK-TIA) Aspirin Trial]. In ECST and NASCET, we also determined the relationship between blood pressure and stroke risk in patients with unilateral carotid occlusion and patients with bilateral > or =70% carotid stenosis. RESULTS: Stroke risk on medical treatment increased with blood pressure in ECST and NASCET, but the relationships were less steep than in the UK-TIA trial. The relationship between blood pressure and stroke risk was not affected by the presence of a unilateral carotid occlusion but was significantly affected by the presence of bilateral carotid stenosis > or =70% (interaction: systolic blood pressure, P=0.002; diastolic blood pressure, P=0.03; pulse pressure, P=0.003). In this group, the relationship was inverted because of the high stroke risks at lower blood pressures. This interaction was not present after carotid endarterectomy and was not present for the risk of myocardial infarction. CONCLUSIONS: The risk of stroke increases with blood pressure in the great majority of patients with symptomatic carotid artery disease, but the relationship is less steep than in other patients with TIA or stroke. The relationship is unaffected by unilateral carotid occlusion alone but is inverted in patients with bilateral > or =70% carotid stenosis, suggesting that aggressive blood pressure lowering may not be advisable in this group. These patients represent only a few percent of all patients with TIA or stroke but have a high risk of recurrent stroke.

Preoperative oral B vitamins prevent nitrous oxide-induced postoperative plasma homocysteine increases.

UNLABELLED: Nitrous oxide increases total homocysteine (tHcy) plasma levels, which are associated with an increase in perioperative myocardial ischemia. We designed this study to determine whether oral B vitamins, which are cofactors in homocysteine metabolism, can prevent nitrous oxide anesthesia-induced tHcy increases in patients undergoing elective surgery scheduled to last longer than 3 h. Fifty-three patients presenting for elective revision knee or hip arthroplasty received in random, double-blinded fashion oral vitamin B complex (folate 2.5 mg, B(6) 25 mg, and B(12) 500 microg) or placebo daily for 1 wk before surgery. Anesthesia was induced with propofol and maintained with an opioid, isoflurane, and nitrous oxide/oxygen (inspired nitrous oxide >50%). Blood samples for measurement of tHcy concentration were obtained at study enrollment, before induction, on arrival in the postanesthesia care unit, and on Day 5. Fourteen patients had their surgery rescheduled after taking their vitamins and were removed from the study. The Placebo group had a mean increase in tHcy concentration from baseline of 15% +/- 31% compared with the Vitamin group, which had an initial decrease of 9.1% +/- 11% (P = 0.035). This was maintained throughout the 5-day study period. The use of an oral B vitamin complex prevented the increase in postoperative tHcy by nitrous oxide. IMPLICATIONS: The use of nitrous oxide anesthesia increases postoperative homocysteine concentrations and associated myocardial ischemia. This study indicates that a 1-wk course of oral B vitamins can prevent the increase in homocysteine from nitrous oxide, and, by implication, myocardial ischemia as well.

Patients with atherosclerotic vascular disease: how low should plasma homocyst(e)ine levels go?

Plasma homocyst(e)ine level is a strong independent risk factor for vascular disease. The spelling of homocyst(e)ine reflects that what is measured, and what constitutes the risk factor; it includes homocysteine, homocystine (the dimer of homocysteine) and mixed cysteine-homocysteine disulfide. Homocyst(e)ine levels above 10.2 micro mol/L are associated with a doubling of coronary risk, and levels above 20 micro mol/L are associated with a 9.9-fold increase in risk compared with levels below 9 micro mol/L. The mechanisms by which homocyst(e)ine promotes vascular disease include increased thrombosis, consumption of nitric oxide, endothelial injury, and reduced thrombolysis. Homocyst(e)ine is an independent predictor of carotid atherosclerosis. Vitamin therapy with folate, pyridoxine (vitamin B(6)), and cyanocobalamin (vitamin B(12)) reduces blood levels of homocyst(e)ine, improves endothelial function, reduces levels of fibrinogen and lipoprotein(a), improves thrombolysis, and in uncontrolled clinical observation, leads to regression of carotid plaque. These lines of evidence support a causal relationship between homocyst(e)ine and atherosclerosis, and suggest that in patients with vascular disease, an appropriate target level for therapy may be below 9 or 10 micro mol/L. Randomized controlled studies are under way to determine whether vitamin therapy is effective in secondary prevention of myocardial infarction and stroke.

Nitrous oxide-induced increased homocysteine concentrations are associated with increased postoperative myocardial ischemia in patients undergoing carotid endarterectomy.

UNLABELLED: Nitrous oxide anesthesia causes increased postoperative plasma homocysteine levels. Acute increases in plasma homocysteine are associated with impaired endothelial function and procoagulant effects. This nitrous oxide-induced plasma homocysteine increase may therefore affect the risk of perioperative cardiovascular events. This prospective, randomized study was therefore designed to evaluate the effect of nitrous oxide anesthesia and postoperative plasma homocysteine levels on myocardial ischemia in patients undergoing carotid endarterectomy. After institutional review board approval and written informed consent, 90 ASA Class I-III patients presenting for elective carotid endarterectomy were randomized to receive general anesthesia with or without nitrous oxide. Prior to induction, on arrival in the postanesthesia care unit, and after 48 h, blood samples were obtained for homocysteine analysis. Three hours prior to induction and for 48 h postoperatively patients were monitored by a three-channel, seven-lead Holter monitor. Postoperatively in the postanesthesia care unit and at 48 h the nitrous oxide group had increased mean plasma homocysteine concentrations of 15.5 +/- 5.9 and 18.8 +/- 14.7 when compared with the nonnitrous group of 11.4 +/- 5.2 and 11.3 +/- 4.0 micromol/L, P: < 0.001. The nitrous oxide group had an increased incidence of ischemia (46% vs. 25%, P: < 0.05), significantly more ischemia (63 +/- 71 vs. 40 +/- 68 min, P: < 0.05), had more ischemic events (82 vs. 53, P: < 0.02), and had more ischemic events lasting 30 min (23 vs. 14, P: < 0.05) than the nonnitrous group. This study reconfirmed that intraoperative nitrous oxide is associated with postoperative increases in plasma homocysteine concentration. This was associated with an increase in postoperative myocardial ischemia. IMPLICATIONS: Use of nitrous oxide during carotid artery surgery induces increases in postoperative plasma homocysteine concentration and is associated with increases in postoperative myocardial ischemia.

Infection-susceptibility alleles of mannose-binding lectin are associated with increased carotid plaque area.

The MBL gene, encoding mannose-binding lectin, determines interindividual variation in susceptibility to certain infectious agents, such as Chlamydia pneumoniae. We examined whether infection-susceptibility alleles of MBL, called "non-A alleles," would be associated with increased carotid plaque area (CPA), an intermediate phenotype of atherosclerosis. In 164 subjects, we measured CPA with 2-dimensional ultrasound. We also determined traditional atherosclerosis risk factors and genotyped all subjects for MBL codons 52, 54, and 57. We used ANOVA to determine sources of variation for CPA and tested the hypothesis that the presence of a single MBL non-A "infection-susceptibility" allele was associated with increased CPA; 45.7% of subjects had at least one non-A allele. ANOVA showed that CPA was significantly associated with MBL genotype, age, smoking, hypertension, and hyperlipidemia (P < 0.05). When MBL was used as the sole independent variable in the regression analysis, the association with CPA was even more significant (P = 0.009). Subjects with at least one MBL non-A allele had significantly higher CPA than subjects homozygous for the MBL A allele and were significantly more likely to have CPA in excess of the sample median. Thus, infection-susceptibility alleles of MBL were associated with increased CPA in this study sample; these alleles may be a determinant of interindividual differences in atherosclerosis risk.

Low-dose and high-dose acetylsalicylic acid for patients undergoing carotid endarterectomy: a randomised controlled trial. ASA and Carotid Endarterectomy (ACE) Trial Collaborators.

BACKGROUND: Endarterectomy benefits certain patients with carotid stenosis, but benefits are lessened by perioperative surgical risk. Acetylsalicylic acid lowers the risk of stroke in patients who have experienced transient ischaemic attack and stroke. We investigated appropriate doses and the role of acetylsalicylic acid in patients undergoing carotid endarterectomy. METHODS: In a randomised, double-blind, controlled trial, 2849 patients scheduled for endarterectomy were randomly assigned 81 mg (n=709), 325 mg (n=708), 650 mg (n=715), or 1300 mg (n=717) acetylsalicylic acid daily, started before surgery and continued for 3 months. We recorded occurrences of stroke, myocardial infarction, and death. We compared patients on the two higher doses of acetylsalicylic acid with patients on the two lower doses. FINDINGS: Surgery was cancelled in 45 patients, none were lost to follow-up by 30 days, and two were lost by 3 months. The combined rate of stroke, myocardial infarction, and death was lower in the low-dose groups than in the high-dose groups at 30 days (5.4 vs 7.0%, p=0.07) and at 3 months (6.2 vs 8.4%, p=0.03). In an efficacy analysis, which excluded patients taking 650 mg or more acetylsalicylic acid before randomisation, and patients randomised within 1 day of surgery, combined rates were 3.7% and 8.2%, respectively, at 30 days (p=0.002) and 4.2% and 10.0% at 3 months (p=0.0002). INTERPRETATION: The risk of stroke, myocardial infarction, and death within 30 days and 3 months of endarterectomy is lower for patients taking 81 mg or 325 mg acetylsalicylic acid daily than for those taking 650 mg or 1300 mg.

Plasma homocyst(e)ine concentration, but not MTHFR genotype, is associated with variation in carotid plaque area.

BACKGROUND AND PURPOSE: Elevated plasma homocyst(e)ine [H(e)] concentration is associated with premature atherosclerosis. A common cause of elevated plasma H(e) concentration is a thermolabile mutation (677T) in the gene encoding methylenetetrahydrofolate reductase (MTHFR). We sought to determine whether plasma H(e) concentration or MTHFR genotype would be more strongly associated with carotid plaque area (CPA), a potential intermediate phenotype of atherosclerosis. METHODS: In 307 subjects who were ascertained through a premature atherosclerosis clinic, we measured CPA with 2-dimensional ultrasound and also determined traditional atherosclerosis risk factors, in addition to plasma H(e) concentration and MTHFR genotypes. RESULTS: We found that the frequency of the MTHFR 677T allele was 0.363 in this sample. Mean plasma H(e) concentration was significantly higher in 677T/T homozygotes than in 677T/C heterozygotes and 677C/C homozygotes (17. 1+/-13.7 versus 13.5+/-6.1 versus 12.6+/-5.9 micromol/L, respectively, P<0.001). Analysis of variance showed that CPA was significantly associated with age, sex, smoking, diabetes, hypertension, and hyperlipidemia (each P<0.05). When plasma H(e) concentration was included in the model, it was significantly associated with CPA (P<0.05). However, when the MTHFR genotype was included in the model, it was not associated with CPA (P=0.50). Furthermore, there was a significant correlation of CPA with plasma H(e) (r=0.23, P<0.0001). However, the mean CPA did not differ between subjects according to genotype. CONCLUISONS: Thus, plasma H(e), but not MTHFR genotype, is significantly associated with carotid atherosclerosis, suggesting that the biochemical test may be sufficient to identify patients who may be at increased risk of atherosclerosis through this mechanism.

Benefit of carotid endarterectomy in patients with symptomatic moderate or severe stenosis. North American Symptomatic Carotid Endarterectomy Trial Collaborators.

BACKGROUND: Previous studies have shown that carotid endarterectomy in patients with symptomatic severe carotid stenosis (defined as stenosis of 70 to 99 percent of the luminal diameter) is beneficial up to two years after the procedure. In this clinical trial, we assessed the benefit of carotid endarterectomy in patients with symptomatic moderate stenosis, defined as stenosis of less than 70 percent. We also studied the durability of the benefit of endarterectomy in patients with severe stenosis over eight years of follow-up. METHODS: Patients who had moderate carotid stenosis and transient ischemic attacks or nondisabling strokes on the same side as the stenosis (ipsilateral) within 180 days before study entry were stratified according to the degree of stenosis (50 to 69 percent or <50 percent) and randomly assigned either to undergo carotid endarterectomy (1108 patients) or to receive medical care alone (1118 patients). The average follow-up was five years, and complete data on outcome events were available for 99.7 percent of the patients. The primary outcome event was any fatal or nonfatal stroke ipsilateral to the stenosis for which the patient underwent randomization. RESULTS: Among patients with stenosis of 50 to 69 percent, the five-year rate of any ipsilateral stroke (failure rate) was 15.7 percent among patients treated surgically and 22.2 percent among those treated medically (P=0.045); to prevent one ipsilateral stroke during the five-year period, 15 patients would have to be treated with carotid endarterectomy. Among patients with less than 50 percent stenosis, the failure rate was not significantly lower in the group treated with endarterectomy (14.9 percent) than in the medically treated group (18.7 percent, P=0.16). Among the patients with severe stenosis who underwent endarterectomy, the 30-day rate of death or disabling ipsilateral stroke persisting at 90 days was 2.1 percent; this rate increased to only 6.7 percent at 8 years. Benefit was greatest among men, patients with recent stroke as the qualifying event, and patients with hemispheric symptoms. CONCLUSIONS: Endarterectomy in patients with symptomatic moderate carotid stenosis of 50 to 69 percent yielded only a moderate reduction in the risk of stroke. Decisions about treatment for patients in this category must take into account recognized risk factors, and exceptional surgical skill is obligatory if carotid endarterectomy is to be performed. Patients with stenosis of less than 50 percent did not benefit from surgery. Patients with severe stenosis (> or =70 percent) had a durable benefit from endarterectomy at eight years of follow-up.

Effects of substituting dietary soybean protein and oil for milk protein and fat in subjects with hypercholesterolemia.

OBJECTIVES: To determine whether, in individuals with hypercholesterolemia, substituting dietary soybean products for cows' milk products improves the plasma lipid profile and whether any change in the profile is due partially to soy oil. DESIGN: Randomized 3-treatment crossover trial. SETTING: Family practice clinics and an outpatient clinic in London, Ont. PARTICIPANTS: Seventeen healthy men and 17 healthy women with elevated plasma levels of total and low-density-lipoprotein (LDL) cholesterol and with normal plasma levels of triglycerides. INTERVENTIONS: Participants incorporated into their normal diet either 2% cows' milk products, soybean products or a combination of skim milk products and soy oil, each over period of 4 weeks, with 22-week wash-out periods. Plasma lipid profile, blood pressure and body weight were assessed after each dietary and wash-out period. OUTCOME MEASURES: Plasma levels of total and lipoprotein cholesterol, plasma levels of triglycerides, apolipoprotein B and A1 levels, blood pressure and plasma lipid peroxidation. RESULTS: The change in diet had no effect on body mass index, levels of apolipoproteins B and A1 and most plasma lipids. During the soybean period, the subjects' mean level of high-density-lipoprotein (HDL) cholesterol increased 9% (p < 0.04) and their mean LDL/HDL cholesterol ratio decreased 14% (p < 0.007). These effects were less pronounced during the skim milk/soy oil period. In the 24 subjects with the highest initial LDL cholesterol level and LDL/HDL cholesterol ratio, the mean LDL cholesterol level decreased 11% after the soybean period. In all subjects, changes in the LDL/HDL cholesterol ratio induced by a soybean diet were negatively correlated with the initial LDL/HDL cholesterol ratio and positively correlated with the initial HDL cholesterol level. CONCLUSIONS: In people with hypercholesterolemia, the plasma lipid profile improved after treatment with a soybean-product diet, and this improvement was partially due to soy oil. The degree of responsiveness was associated with initial risk factors for coronary artery disease.

Psychological stress and the progression of carotid artery disease.

BACKGROUND: We examined the relation between cardiovascular reactivity (the response of the cardiovascular system to psychological stress) and the severity and progression of carotid atherosclerosis. METHODS: Using duplex ultrasonography, we measured the change in the area of all detectable plaques in the extracranial carotid arteries during 2 years. Cardiovascular reactivity was assessed by measuring changes in hemodynamics during a frustrating cognitive task (the Stroop Color Word Interference Task). Established risk factors for atherosclerosis were measured by interviewing patients, a physical examination, and blood assays for 351 subjects with a wide range of types of atherosclerotic disease. RESULTS: Atherosclerotic plaques were present in the carotid arteries of 273 (78%) subjects. In a forward stepwise multiple regression analysis, it was found that greater age (beta = 0.46), a history of hypertension (beta = 0.20), use of lipid level-lowering agents (beta = 0.18), a longer history of smoking (beta = 0.13), a larger cholesterol:high-density lipoprotein ratio (beta = 0.13), a smaller change in heart rate during the task (beta = -0.12), and a higher resting systolic blood pressure (SBP; beta = 0.11) were associated significantly with a greater plaque area (R2 = 0.35). In 136 untreated subjects who were followed up for 2 years, a greater change in SBP during the task (beta = 0.28), a higher total cholesterol: high-density lipoprotein ratio (beta = 0.23), a shorter resting preejection period (beta = -0.19), and a lower body mass index (beta = -0.17) were significant predictors of the change in atherosclerosis, after controlling for age and initial plaque area in a stepwise multiple regression analysis (R2 = 0.24). CONCLUSIONS: These results support the hypothesis that hemodynamic responses under conditions of mental stress may influence the progression of atherosclerosis.

Cerebral consequences of hypertension: where do they lead?

BACKGROUND: Hypertension is a major risk factor for two distinct kinds of vascular problems: complications of atherosclerosis including myocardial and cerebral infarction, as well as complications of hypertensive small vessel disease, including renal failure, intracerebral hemorrhage and lacunar infarctions. If these consequences were solely due to elevation of blood pressure, they should be equally prevented by treatments that reduce blood pressure. OBSERVATION: The installation of a computed tomography (CT) scanner in our hospital before the initiation of a large study by the Department of Family Medicine markedly increased the detection and treatment of hypertension in our region. As a result, we found that treating high blood pressure prevented arteriolar but not atherosclerotic strokes. HYPOTHESIS: Our observation raises questions about the nature of hypertension, which can be regarded as a disorder of fluid energy, with arteriolar consequences being due to elevated pressure, and atherosclerotic consequences being related to kinetic energy, derived from pressure energy when flow patterns become disturbed. It is hypothesized that the remodelling of arteries to conform to flow patterns may be driven by increased nitric oxide at regions of high shear, leading the artery to 'grow away' from high shear, whereas endothelin released in regions of low shear may cause the artery to 'fill in' the low shear region. This may, in part, explain the protection that women enjoy until menopause, as estrogen increases nitric oxide release and probably reduces endothelin production in the endothelium. PREDICTORS OF ATHEROSCLEROSIS PROGRESSION: The pressure kinetic construct has led to studies on the effects of antihypertensive drugs on flow disturbances in arteries leading, in turn, to studies on the relationship between mental stress and atherosclerosis. We have shown that the rise in blood pressure during mental stress is a stronger predictor of atherosclerosis progression than any of the standard risk factors such as age, sex, blood pressure, smoking, lipids or diabetes. The regression model used to make explicit the effect of stress responses on atherosclerosis not only offers a powerful new way to identify new causes of atherosclerosis, but also leads to a new quantitative trait, the rate of progression of atherosclerosis not explained by the Framingham risk factors. This trait, "unexplained atherosclerosis progression', in combination with three-dimensional ultrasound measurement of atherosclerosis, may lead to the discovery of new genes for atherosclerosis and thus help to manage the genetic heterogeneity of this disease.

Intramuscular administration of iron during long-term chelation therapy with 2,3-dimercaptosuccinic acid in a man with severe lead poisoning.

2,3-Dimercaptosuccinic acid (DMSA) an investigational chelant structurally similar to dimercaptopropanol (BAL), offers the advantage of not depleting iron stores on which basis it would not seem to form a toxic chelate with iron. We report the case of a man with a formidable body burden of lead (Pb) and depleted iron stores who was given iron intramuscularly during a defined period of long-term retreatment with DMSA. Initiation of retreatment with DMSA, 30 mg/kg/day given orally in three divided doses for the first 7 days markedly enhanced Pb diuresis, entailed a pronounced fall in blood Pb and abolished symptoms of Pb poisoning. Continuation of retreatment with two-thirds the initial DMSA dose for an added 15 days maintained blood Pb at sustained low levels. Iron sorbitol administered intramuscularly during this period in individual doses of 100 mg of elemental iron given 3 days apart to a conservative total of 400 mg produced no untoward effects, suggesting that a toxic chelate between iron and DMSA was not formed. Serum ferritin entered the normal range and there was virtually an immediate significant decrease in erythrocyte protoporphyrin. Together with discernible increases in haemoglobin, haematocrit and MCV, this pointed to enhanced iron utilization. Since iron utilization is curtailed by high concentrations of Pb, the immediacy and magnitude of the post-chelation rebound in blood Pb precluded iron administration at any other stage. From these data, DMSA emerges as a uniquely versatile new chelant. Suitable for long-term administration, it permits the simultaneous parenteral administration of iron during dose-related sustained decreases in blood Pb.

Spectrum of benign intracranial hypertension in children and adolescents.

A review of the most recent 23 cases of benign intracranial hypertension (BIH), admitted to the War Memorial Children's Hospital in London, Ontario, provided a compendium of the clinical manifestations of this disorder in children and adolescents. Although CT scanning lets one feel more secure in making such a diagnosis, pitfalls still exist. The sex ratio was 11 males to 12 females. Age groupings were: 0-6 years (2 patients); 7-12 years (10); 13-17 years (11). No postviral etiologies were encountered in patients more than 13 years of age. In only 6 cases could no definite etiology be established. Of great importance was the recognition of the condition in 12 patients who did not have papilledema. Elevated intracranial pressure was proven in 8 of these by lumbar CSF pressure monitoring, in 1 by lumbar punctures and in 1 infant with split cranial sutures. Absence of papilledema was confirmed by ophthalmological examination. Transient visual obscurations were very common in this group. In 6 patients, persistent signs and symptoms in spite of vigorous drug therapy prompted lumboperitoneal shunting, with immediate relief of symptoms in all. In only 1 case has the diagnosis of BIH proven to be in error. A warning leak from an aneurysm caused papilledema and headache, and a normal CT scan supported the diagnosis until the patient had a major hemorrhage weeks later. BIH has a variety of causes in children and adolescents, and papilledema is not a prerequisite for diagnosis.

Doppler flow maps of the carotid artery compared with the findings on angiography.

One noninvasive method of evaluating the condition of the carotid arteries is by the Echoflow Doppler device, which produces colour-coded images of the flow pattern in the arteries. Normal velocities are represented in red, accelerated flow in yellow and turbulences in blue. The authors present the results of Echoflow studies in 317 patients who also underwent cerebral angiography. Of 660 normal carotid vessels, 21 showed appreciable abnormalities on Echoflow study (false positive 3.2%). Of 87 vessels with stenosis of 50% or more, the Echoflow study showed normal flow in 26 (false negative 29.9%). The Echoflow study indicated no abnormalities in 3 of 22 patients with severe stenosis (more than 80%) (false negative 13.6%). Of nine patients with carotid occlusion, the Echoflow study gave normal findings in one (false negative 11.1%). Sensitivity was 70.1%, specificity was 96.9%, with a positive predictive accuracy of 93.9%. Sources of error include misidentification of arteries, signal attenuation (acoustic shadow), hemodynamic changes and timing of the Echoflow study relative to angiography. Combined studies with B-mode ultrasonography and spectral analysis of the Doppler signal should reduce error. These studies should not be used to replace angiography, but to help select for angiography patients for whom the study might be contraindicated because of advanced age or cardiac disease.