Robert Barndt

Precipitants of Brain Infarction Roles of Preceding Infection/Inflammation and Recent Psychological Stress

BACKGROUND AND PURPOSE Antecedent febrile infection and psychological stress are described as predisposing risk factors for brain infarction. We examined the temporal relationship between preceding infection/inflammation and stroke onset as well as the role of recent psychological stress as a potential precipitant for brain infarction. METHODS In this case-control study, a standardized evaluation including a signs/symptoms-based questionnaire was used to characterize the prevalence and timing of recent prior (< 1 month) infectious and inflammatory syndromes in 37 adults with acute brain infarction, 47 community control subjects, and 34 hospitalized nonstroke neurological patient controls. Recent psychological stress was measured with scales of stressful life events and negative affect. RESULTS The prevalence of infection/inflammation was significantly higher in the stroke group only within the preceding 1 week compared with either community control subjects (13/37 versus 6/47, P < .02) or hospitalized neurological patient controls (3/34, P < .02). Upper respiratory tract infections constituted the most common type of infection. A substantial proportion of stroke patients with preceding (< 1 week) infection/inflammation (5/13) had no accompanying fever or chills. There were no significant differences between the stroke and control groups in the levels of stressful life events within the prior 1 month or in negative-affect scale scores within the prior 1 week. CONCLUSIONS Our data suggest that both febrile and nonfebrile infectious/inflammatory syndromes may be a common predisposing risk factor for brain infarction and that the period of increased risk is confined within a brief temporal window of less than 1 week. Results of this study argue against a role for recent psychological stress as a precipitant for cerebral infarction.

Impairments of the Protein C System and Fibrinolysis in Infection-Associated Stroke

BACKGROUND AND PURPOSE Infection/inflammation appears to be an important predisposing risk factor for brain infarction, but little is known regarding underlying molecular mechanisms. We examined the hypothesis that patients with brain infarction preceded by infection/inflammation within 1 week could be identified by a distinctive procoagulant laboratory profile characterized by abnormalities in the protein C system and endogenous fibrinolysis. METHODS We performed a case-control study examining the relationship between preceding systemic infectious/inflammatory syndromes and selected immunohematologic variables in 36 patients with acute brain infarction and 81 control subjects (community control subjects [n = 47] and hospitalized nonstroke neurological patient controls [n = 34]). RESULTS The stroke group had a lower mean level of the circulating antithrombotic enzyme activated protein C (APC) (4.33 +/- 0.34% [log-transformed percentage of control value, mean +/- SD]) than community control subjects (4.51 +/- 0.27%, P < .02) or hospitalized neurological patient controls (4.57 +/- 0.31%, P < .005). The lowest circulating APC levels were found in the stroke group with antecedent infection/inflammation within 1 week preceding index brain infarction (4.23 +/- 0.4%, n = 12). Within the stroke group, circulating APC levels were inversely related to IgG isotype anticardiolipin antibody titers (r = -.55, P < .001). Only the stroke group with infection/inflammation within 1 week had elevated plasma C4b binding protein compared with control subjects (141 +/- 61% versus 112 +/- 44%, P < .05). Stroke patients with antecedent infection/inflammation had a distinctively lower ratio of active tissue plasminogen activator to plasminogen activator inhibitor (0.11 +/- 0.04, n = 9) than other stroke patients (0.19 +/- 0.06, n = 9, P < .01) and control subjects (0.22 +/- 0.16, n = 17, P < .02). CONCLUSIONS Impairments in the protein C pathway and endogenous fibrinolysis may contribute to the increased risk for brain infarction after recent (< or = 1 week) infection/inflammation. A decrease in the circulating anticoagulant APC may be related to elevated antiphospholipid antibody titers.

Measurement of atherosclerotic luminal irregularity and obstruction by radiographic densitometry.

This report describes a procedure to quantify stenosis and to detect enface plaques in single plane angiograms. We derived an optical density function proportional to local arterial chord length from arteriographs over a wide range of conditions. Standard radiographs were made of silicone rubber bolus used as the radiopaque medium in cadaver arteries. Replicate arterial casts filled with iodine-bearing contrast medium were radiographed for comparison. Identical atherosclerotic areas in both film sets were scanned with a microdensitometer and vessel chord lengths used to construct arterial cross sections for comparison with vessel casts. Cross-sectional areas derived from cadaver and phantom films were highly correlated with those derived from cast slices (r = 0.997). Thus, luminal cross-sectional areas were accurately estimated independent of plaque location, and accuracy of chord length measurement was +/- 0.28 mm in vessels four to 10 mm in diameter.

Prevalence of asymptomatic femoral artery atheromas in hyperlipoproteinemic patients

Abstract Atheroma prevalence in hyperlipoproteinemic patients was evaluated by femoral angiography. The femoral arteries of 29 men (20–51 years of age) were injected with contrast medium using an 18 gauge needle. Eighteen patients were post myocardial infarction, two had prior claudication. Angiography caused no vascular complications. The films were graded using the International Atherosclerosis Grading System as previously applied to angiograms and validated by autopsy studies. Percent of arterial edge involvement (%AEI) was measured and was reproducible on double blind testing (γ = 0.991, SEE=4.4 %). Grade 1, 2 or 3 lesions were distinguishable in 28 of 29 patients. An exponential relationship was found between %AEI and age in 17 Type II patients (γ = 0.844, P in vivo .

Discrimination of human arterial pathology by computer processing of angiograms for serial assessment of atherosclerosis change

Abstract Femoral angiograms were made in 21 cadavers under conditions which simulated clinical films. Then these arteries were excised, laid open, and color photographed along side of corresponding casts of the arterial lumen. Twenty-seven segments, 5 cm long, were classified as exemplary of normal vessel, uncomplicated stenosis, or hemorrhagic ulceration. The corresponding angiogram images of these arterial segments were digitized and processed to yield outlines of the vessel edges, and from these, computer measures were developed which described how these outlines deviated from ideal ones. Six of these measures were selected by means of stepwise discriminant analysis to distinguish the type of disease along the 27 exemplary segments, and 96% were correctly classified. Computer processing of angiograms shows promise for discriminating the nature of atherosclerotic lesions.

Prevalence and Distribution of Femoral Atheromas in Human Hyperlipoproteinemia, Type II and IV

The prevalence of femoral atherosclerotic lesions in Type II and Type IV hyperlipoproteinemia has been determined by performing Limited Femoral Angiography in 18 Type II and 10 Type IV patients attending a clinic for therapy of hyperlipoproteinemia. Patients studied were those willing to volunteer for femoral angiography as an experimental procedure for determination of lesion prevalence and possible guide to evaluation of their therapy. Written informed consent was obtained from all prior to angiography.

A new three-dimensional postmortem method to study the topography of atherosclerosis using profilometry

The examination of high resolution casts of atherosclerotic arteries with a surface profile projector provides a 3-dimensional method for the measurement of atherosclerotic lesions. Lesions recorded on casts are found to predict gross and microscopic pathology. The contrast and magnification provided afford a continuum of atherosclerotic grades from the microscopic to macroscopic range. Lesion size and grade can be related to the geometry of the arterial lumen.