Longitudinal evaluation of diffusion tensor imaging and cognition in systemic lupus erythematosus.

Objective This pilot study aimed to examine longitudinal changes in brain structure and function in patients with systemic lupus erythematosus (SLE) using diffusion tensor imaging (DTI) and neuropsychological testing. Methods Fifteen female SLE patients with no history of major neuropsychiatric (NP) manifestations had brain magnetic resonance imaging (MRI) with DTI at baseline and approximately 1.5 years later. At the same time points, a standardized battery of cognitive tests yielding a global cognitive impairment index (CII) was administered. At baseline, the SLE patients had mean age of 34.0 years (SD = 11.4), mean education of 14.9 years (SD = 2.1), and mean disease duration of 121.5 months (SD = 106.5). The MRI images were acquired with a 3T GE MRI scanner. A DTI sequence with 33 diffusion directions and b-value of 800 s/mm2 was used. Image acquisition time was about 10 minutes. Results No significant change in cognitive dysfunction (from the CII) was detected. Clinically evaluated MRI scans remained essentially unchanged, with 62% considered normal at both times, and the remainder showing white matter (WM) hyperintensities that remained stable or resolved. DTI showed decreased fractional anisotropy (FA) and increased mean diffusivity (MD) in bilateral cerebral WM and gray matter (GM) with no major change in NP status, medical symptoms, or medications over time. Lower FA was found in the following regions: left and right cerebral WM, and in GM areas including the parahippocampal gyrus, thalamus, precentral gyrus, postcentral gyrus, angular gyrus, parietal lobe, and cerebellum. Greater MD was found in the following regions: left and right cerebral WM, frontal cortex, left cerebral cortex, and the putamen. Conclusions This is the first longitudinal study of DTI and cognition in SLE, and results disclosed changes in both WM and GM without cognitive decline over an 18-month period. DTI abnormalities in our participants were not associated with emergent NP activity, medical decline, or medication changes, and the microstructural changes developed in the absence of macrostructural abnormalities on standard MRI. Microstructural changes may relate to ongoing inflammation, and the stability of cognitive function may be explained by medical treatment, the variability of NP progression in SLE, or the impact of cognitive reserve.

Cardiopulmonary correlates of cognition in systemic lupus erythematosus.

OBJECTIVE: We aimed to evaluate the relationship between cognitive dysfunction and lung function, exercise endurance, and self-reported activity levels in patients with systemic lupus erythematosus (SLE). BACKGROUND: Cognitive dysfunction is present in 20%-60% of SLE patients. No studies to date have investigated the inter-relationships between cardiopulmonary factors and cognition in this population. METHODS: Thirty-seven SLE patients without overt neuropsychiatric histories and 16 healthy controls completed neuropsychological testing, measures of lung function, exercise capacity (distance walked during a timed walk test,(1) maximal oxygen uptake(2)), and exercise questionnaires. RESULTS: Thirty-two percent of SLE patients demonstrated cognitive impairment. Cognitive impairment was correlated with Six-Minute Walk Distance (6MWD) (r = 0.37, p = 0.02) and certain measures of lung function. Also, in SLE patients, self-reported physical activity was correlated with 6MWD (p = 0.012), but none of the more complex measures of physical activity (VO2max). CONCLUSIONS: Patients with mild SLE disease activity have cognitive dysfunction associated with certain objective markers of exercise capacity and activity levels. The lack of associations between self-report activity and VO2max suggests the possibility that multiple factors mediate the relationships between perceived and actual physical ability. Additional studies are needed to better understand the relationship between cognition and physical activity in patients with SLE.

A Biomechanical Analysis of Tibial Fixation Methods in Hamstring-Graft Anterior Cruciate Ligament Reconstruction.

Background: There are conflicting results on the biomechanical properties of tibial fixation devices in anterior cruciate ligament reconstruction. The objective of this study is to compare the initial biomechanical properties of tibial fixation in hamstring-graft ACL reconstruction with interference screw, suspension button, and Tape Locking ScrewTM devices. We hypothesized there are no differences in the initial biomechanical properties of these three tibial fixation techniques. Methods: Twenty-one fresh-frozen porcine tibiae were equally divided into three groups of seven tibiae to evaluate the fixation of human hamstring tendon grafts with interference screw, suspension button, or Tape Locking Screw fixation. Using a servohydraulic materials testing system, each graft was subjected to 500 cycles of loading followed by a monotonic failure test. Results: Interference screw fixation demonstrated significantly lower cyclic displacement (1.28 ± 0.73 mm) than the other groups fixated with either a suspension button device (2.54 ± 0.27 mm, p = 0.003) or a Tape Locking Screw (2.32 ± 0.42 mm, p = .009), and a significantly greater cyclic stiffness (212.19 ± 40.30 N/mm) than the Tape Locking Screw (137.64 ± 26.17 N/mm, p = 0.002). The interference screw also demonstrated significantly higher pullout stiffness (166.83 ± 23.22 N/mm) than the suspension button (112.78 ± 24.14 N/mm, P = 0.002) and Tape Locking Screw (109.11 ± 12.91 N/mm, P = 0.0002). Conclusions: Tibial fixation with an interference screw demonstrated superior biomechanical properties for cyclic testing compared to the suspension button and Tape Locking Screw. Load to failure did not differ between groups, and there were no significant biomechanical differences between the suspension button and Tape Locking Screw fixation devices. Clinical Relevance: Despite the initial biomechanical differences, all three fixation devices exhibited mean loads to failure and cyclic displacements below clinically relevant thresholds of failure. These data suggest all three fixation methods are viable options for achieving a functional ACL reconstruction.Level of Evidence: V.

Functional Magnetic Resonance Imaging of Working Memory and Executive Dysfunction in Systemic Lupus Erythematosus and Antiphospholipid Antibody-Positive Patients.

OBJECTIVE: Standardized cognitive tests and functional magnetic resonance imaging (fMRI) studies of systemic lupus erythematosus (SLE) patients demonstrate deficits in working memory and executive function. These neurobehavioral abnormalities are not well studied in antiphospholipid syndrome, which may occur independently of or together with SLE. This study compares an fMRI paradigm involving motor skills, working memory, and executive function in SLE patients without antiphospholipid antibody (aPL) (the SLE group), aPL-positive non-SLE patients (the aPL-positive group), and controls. METHODS: Brain MRI, fMRI, and standardized cognitive assessment results were obtained from 20 SLE, 20 aPL-positive, and 10 healthy female subjects with no history of neuropsychiatric abnormality. RESULTS: Analysis of fMRI data showed no differences in performance across groups on bilateral motor tasks. When analysis of variance was used, significant group differences were found in 2 executive function tasks (word generation and word rhyming) and in a working memory task (N-Back). Patients positive for aPL demonstrated higher activation in bilateral frontal, temporal, and parietal cortices compared to controls during working memory and executive function tasks. SLE patients also demonstrated bilateral frontal and temporal activation during working memory and executive function tasks. CONCLUSION: Compared to controls, both aPL-positive and SLE patients had elevated cortical activation, primarily in the frontal lobes, during tasks involving working memory and executive function. These findings are consistent with cortical overactivation as a compensatory mechanism for early white matter neuropathology in these disorders.

Identification of quantifiable hemodynamic factors in the assessment of cerebral aneurysm behavior. On behalf of the Subcommittee on Biorheology of the Scientific and Standardization Committee of the ISTH.

Previous experimental and theoretical studies on the hemodynamics of saccular intracranial aneurysms have provided evidence that aneurysms tend to grow, thrombose and rupture when (1) wall shear stress and mural tension are increased compared to normal values, and (2) flow deviates from a laminar unidirectional pattern (for example flow recirculation). Aneurysm wall shear stress, however, is the only hemodynamic factor which has received special attention in terms of estimation. Additional flow-related parameters exist which could potentially bring increased insight into mechanisms for cerebral aneurysm behavior; they could also help categorize the severity of such malformations and design effective intravascular treatment techniques. The purpose of this paper is thus to present an overview of such hemodynamic factors that could assist in determining the geometries which present the greatest risks to patients. These parameters include (1) hemodynamic shear stress, (2) pressure and related stresses, (3) impingement force on the aneurysm wall, (4) inflow rate into the aneurysm, and (5) residence time of blood within the aneurysmal sac. In addition, these factors can also be currently estimated in an in vitro setting.

Computer modeling of intracranial saccular and lateral aneurysms for the study of their hemodynamics.

There is strong evidence indicating hemodynamic stress as an underlying cause for saccular intracranial aneurysm growth, thrombosis, and/or rupture. We examined flow fields encountered in models of cerebral aneurysms having a lateral (originating from the side of an artery, not at a branch point) geometric configuration. Shear stress and pressure gradients acting on aneurysm walls under a variety of flow and geometric conditions were evaluated. For this purpose, a two-dimensional finite-element computer model of lateral aneurysms in a steady-flow state was developed. Three idealized aneurysm shapes were studied, half-spherical, spherical, and pear-shaped. The ostium width of the cerebral aneurysm, relative to the radius of the parent artery and the Reynolds number, were also varied. Maximal shear stresses and maximum pressures (for an ostium width of 2 times the radius of the parent artery) were typically found at the downstream site of the ostium, rather than at the dome of the aneurysm. In general, the highest shear stresses and the lowest pressures (at the distal portion of the ostium) were obtained in the spherical aneurysm, whereas the lowest shear stresses and the highest pressures were found in the half-spherical aneurysm. The location of maximal stresses (shear and pressure) at the distal region of the ostium suggests that growth and/or rupture may well proceed from this point. Such findings are in contrast to the commonly held opinion that aneurysm rupture occurs at the dome. Careful pathological investigation will need to be performed to clarify this finding. The results of this preliminary investigation also indicate that the flow field in lateral aneurysms is highly dependent on a number of factors related to flow and geometric parameters. Geometry seems to be a significant mediator of local magnitudes of stress. Thus, the tendency for growth or thrombosis may be influenced by variations in size or shape.

A model based on dimensional analysis for non-invasive quantification of valvular regurgitation under confined and impinging conditions.

The most descriptive measure of valvular insufficiency is the regurgitant volume. Current techniques for measuring it, however, are invasive and semi-quantitative at best. Cape and colleagues have recently developed a non-invasive technique for the quantitation of regurgitant flows corresponding to free jets cases. This technique is, unfortunately, not applicable to cases of jets constrained and/or impinging on the atrial walls as observed in many cases of mitral regurgitation. The purpose of this paper was therefore to develop an equation based on dimensional analysis, for calculating peak regurgitant flow rates from quantities than can be measured by Doppler ultrasound/echocardiography. The result is an equation for flow rate, Qo, as a function of orifice velocity, Uo, a downstream centerline velocity, Um, at a distance, x, from the orifice, the diameter of the receiving chamber, Dc, and the impingement height, H: Qo = (pi Uo/4)[a(Uo/Um)HcDdc chi e][2/(c+d+e)], where a, c, d and e can be found by multiple linear regressions on pulsed Doppler jet centerline velocity data. The assumptions made in the derivation are such that they should be physiologically applicable. The advantage of this method compared to the previous one is its theoretical justification and ability to quantify accurately peak regurgitant flow rate, and total regurgitant volume.

A model based on dimensional analysis for noninvasive quantification of valvular regurgitation under confined and impinging conditions: in vitro pulsatile flow validation.

A technique is proposed for the noninvasive quantification of regurgitant flows under confined and impinging conditions. Its use requires only the knowledge of the jet orifice velocity, receiving chamber diameter, orifice-to-end wall distance and any downstream jet centerline velocity at a known distance from the orifice. The technique is based on dimensional analysis and provides a prediction of peak regurgitant flow rates. To validate the technique, known physiologic pulsatile flows were pumped through 2- and 4-mm circular orifices at 70 to 150 beats/min, into two different receiving chambers of 51 and 88 mm in diameter. At each heart rate, the peak orifice velocity was varied from 2 to 5 m/s, and the orifice-to-end wall distance was varied from 30 to 93 mm. Centerline velocities were recorded by pulsed Doppler ultrasound and averaged over multiple beats. A dimensional analysis of the parameters of the study provided an equation relating normalized centerline velocity to orifice-to-end wall distance, chamber diameter and downstream location. Statistical modeling of the experimental data was performed to compute the constants involved in this equation. The estimated (i.e., predicted by the technique) peak regurgitant flow rates were found to fall within 10% of the actual values, when centerline velocities were measured over a range of centerline distances from six orifice diameters to 85% of the chamber length. Therefore, the proposed technique provides, for the first time, a quantitative method for calculating valvular regurgitant flow rates under confined and impinging conditions.

Association of renal graft survival with matching at the HLA-DR locus.

The influence of HLA-DR antigen matching in 70 cadaver transplants was studied for up to four years. The overall cumulative renal graft survival at one year was 62 percent, and at two and four years it was 60 percent. The one, two, and four year cumulative graft survival for patients receiving one or two HLA-DR antigen matched grafts was 74 percent, 69 percent, and 69 percent, respectively. In contrast, the one, two, and four year cumulative graft survival for patients receiving zero HLA-DR antigen matched grafts was 51 percent, 47 percent, and 47 percent, respectively. The cumulative graft survival for patients receiving one or two HLA-DR antigen matched grafts was significantly different (p less than 0.05) than for patients receiving zero HLA-DR antigen match grafts. No significant difference in the distribution of other prognostic factors were observed between patients receiving one or two HLA-DR antigen match grafts and patients receiving zero HLA-DR antigen matched grafts. The present authors concluded that matching for HLA-DR antigens exerts an independent beneficial effect on renal graft survival in transplant patients, most of whom have been previously transfused.

Quantification of cardiac jets: theory and limitations.

Jet flows are consequences of many cardiac lesions. With the advent of color Doppler flow mapping, these jet flows can be visualized noninvasively. Currently, an intense effort is underway to quantify cardiac jet flows as a means to assess the severity of jet forming lesions. Two techniques, PISA and jet centerline decay, have been suggested as methods to quantify jet flow volume. Although both techniques are theoretically sound, both formulations are based on ideal flow conditions that may not be completely realized in cardiac chambers. Thus, the complex dynamics of cardiac jet flows must be considered as they may diminish the accuracy of flow rate calculations. However, realistic in vitro experiments that mimic the impact of cardiac flow conditions on converging flows and jets, combined with carefully controlled in vivo testing of both PISA and centerline techniques, may eventually produce clinically useful quantification formulations.