RESUMEN
Differentiation of systemic lupus erythematosus (SLE) from multiple sclerosis (MS) can be challenging, especially when neuropsychiatric (NP) symptoms are accompanied by white matter lesions in the brain. Given the lack of discriminative power of currently applied tools for their differentiation, there is an unmet need for other measures that can aid in distinguishing between the two autoimmune disorders. In this study we aimed at exploring whether brain atrophy measures could serve as markers differentiating MS and SLE. Thirty-seven relapsing-remitting MS and 38 SLE patients with nervous system manifestations, matched according to age and disease duration, underwent 1.5 Tesla magnetic resonance imaging (MRI), including volumetric sequences, and clinical assessment. Voxelwise analysis was performed using ANTS-SyN elastic registration protocol, FSL Randomise and Gamma methods. Cortical and subcortical segmentation was performed with Freesurfer 5.3 pipeline using T1-weighted MPRAGE sequence data. Using MRI volumetric markers of general and subcortical gray matter atrophy and clinical variables, we built a stepwise multivariable logistic diagnostic model to identify MRI parameters that best differentiate MS and SLE patients. We found that the best volumetric predictors to distinguish them were: fourth ventricle volume (sensitivity 0.86, specificity 0.57, area under the curve, AUC 0.77), posterior corpus callosum (sensitivity 0.81, specificity 0.57, AUC 0.68), and third ventricle to thalamus ratio (sensitivity 0.42, specificity 0.84, AUC 0.65). The same classifiers were identified in a subgroup analysis that included patients with a short disease duration. In MS brain atrophy and lesion load correlated with clinical disability, while in SLE age was the main determinant of brain volume. This study proposes new imaging parameters for differential diagnosis of MS and SLE with central nervous system involvement. We show there is a different pattern of atrophy in MS and SLE, and the key structural volumes that are differentially affected include fourth ventricle and posterior section of corpus callosum, followed by third ventricle to thalamus ratio. Different correlation patterns between volumetric and clinical data may suggest that while in MS atrophy is driven mainly by disease activity, in SLE it is mostly associated with age. However, these results need further replication in a larger cohort.
Asunto(s)
Encéfalo/diagnóstico por imagen , Vasculitis por Lupus del Sistema Nervioso Central/diagnóstico por imagen , Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Neuroimagen/métodos , Adolescente , Adulto , Factores de Edad , Atrofia , Encéfalo/patología , Estudios Transversales , Diagnóstico Diferencial , Evaluación de la Discapacidad , Femenino , Humanos , Vasculitis por Lupus del Sistema Nervioso Central/patología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/patología , Valor Predictivo de las Pruebas , Adulto JovenRESUMEN
Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.
Asunto(s)
Trastornos del Conocimiento/diagnóstico por imagen , Cognición , Sustancia Gris/diagnóstico por imagen , Lupus Eritematoso Sistémico/diagnóstico por imagen , Imagen por Resonancia Magnética , Esclerosis Múltiple Recurrente-Remitente/diagnóstico por imagen , Adolescente , Adulto , Atrofia , Ganglios Basales/diagnóstico por imagen , Ganglios Basales/patología , Trastornos del Conocimiento/etiología , Trastornos del Conocimiento/patología , Trastornos del Conocimiento/psicología , Estudios Transversales , Femenino , Sustancia Gris/patología , Humanos , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/patología , Lupus Eritematoso Sistémico/psicología , Masculino , Persona de Mediana Edad , Esclerosis Múltiple Recurrente-Remitente/complicaciones , Esclerosis Múltiple Recurrente-Remitente/patología , Esclerosis Múltiple Recurrente-Remitente/psicología , Pruebas Neuropsicológicas , Valor Predictivo de las Pruebas , Estudios Prospectivos , Psicometría , Factores de Riesgo , Tálamo/diagnóstico por imagen , Tálamo/patología , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Nonimaging transcranial Doppler sonography (TCD) and imaging TCD (TCDI) are used for determination of the risk of stroke in children with sickle cell disease (SCD). The purpose was to compare angle-corrected, uncorrected TCDI, and TCD blood flow velocities in children with SCD. MATERIALS AND METHODS: A total of 37 children (mean age, 7.8 +/- 3.0 years) without intracranial arterial narrowing determined with MR angiography, were studied with use of TCD and TCDI at the same session. Depth of insonation and TCDI mean velocities with and without correction for the angle of insonation in the terminal internal carotid artery (ICA) and middle (MCA), anterior (ACA), and posterior (PCA) cerebral arteries were compared with TCD velocities with use of a paired t test. RESULTS: Two arteries were not found on TCDI compared with 15 not found on TCD. Average angle of insonation in the MCA, ACA, ICA, and PCA was 31 degrees , 44 degrees , 25 degrees , and 29 degrees , respectively. TCDI and TCD mean depth of insonation for all arteries did not differ significantly; however, individual differences varied substantially. TCDI velocities were significantly lower than TCD velocities, respectively, for the right and left sides (mean +/- SD): MCA, 106 +/- 22 cm/s and 111 +/- 33 cm/s versus 130 +/- 19 cm/s and 134 +/- 26 cm/s; ICA, 90 +/- 14 cm/s and 98 +/- 27 cm/s versus 117 +/- 18 cm/s and 119 +/- 23 cm/s; ACA, 74 +/- 24 cm/s and 88 +/- 25 cm/s versus 105 +/- 23 cm/s and 105 +/- 31 cm/s; and PCA, 84 +/- 27 cm/s and 82 +/- 21 cm/s versus 95 +/- 23 cm/s and 94 +/- 20 cm/s. TCD and angle-corrected TCDI velocities were not statistically different except for higher angle-corrected TCDI values in the left ACA and right PCA. CONCLUSION: TCD velocities are significantly higher than TCDI velocities but are not different from the angle-corrected TCDI velocities. TCDI identifies the major intracranial arteries more effectively than TCD.
Asunto(s)
Anemia de Células Falciformes/diagnóstico , Anemia de Células Falciformes/fisiopatología , Velocidad del Flujo Sanguíneo , Arteria Carótida Interna/diagnóstico por imagen , Arterias Cerebrales/diagnóstico por imagen , Ultrasonografía Doppler Transcraneal/métodos , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Platelet angiotensin II (AngII) receptor number has been suggested as a screening test for pregnancy-induced hypertension. However, markedly different false-positive rates have been reported, perhaps the result of differing methods used. We sought therefore to compare the two methods. Platelet AngII receptor number was determined by saturation analysis with computerized curve fitting and specific binding at a single radioligand concentration. The two methods were compared by correlation and by plotting their differences v their means, to determine their limits of agreement. There were significant correlations between the value obtained by saturation analysis and each of the three single ligand concentrations studied (1 nmol/L, P < .001; 500 pmol/L, P < .001; and 250 pmol/L, P < .01). However, for none of the three did the regression line approach the line of equality. Assessment of agreement by comparing differences and means for each subject showed increasing scatter with increasing receptor number and 95% confidence intervals too large to be clinically relevant. We conclude that the receptor number estimated from specific binding at one ligand concentration differs significantly from that obtained by saturation analysis. The limits of agreement of the two methods are wide and we urge caution in the use of single ligand concentration methods for estimating binding site densities.
Asunto(s)
Angiotensina II/sangre , Plaquetas/química , Hipertensión/diagnóstico , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Receptores de Angiotensina/análisis , Adulto , Femenino , Humanos , Preeclampsia/diagnóstico , Embarazo , Ensayo de Unión RadioliganteRESUMEN
1. Quantification of platelet angiotensin II (AII) receptors has been suggested as a screening test for pregnancy-induced hypertension (PIH). Saturation analysis is too technically demanding to screen the requisite numbers and although a simplified method has been proposed, it has not been validated against saturation. This study sought to compare the two methods. 2. Platelet AII receptor number was determined by saturation analysis and from the specific binding at each of three radioligand concentrations. The two methods were compared by correlation and by plotting their differences against their means to determine limits of agreement. 3. Significant correlations were observed at all three radioligand concentrations; however, none of the regression lines approached the line of equality. There was increasing scatter as receptor number increased and 95% confidence intervals were too large to be clinically useful. 4. From this study it is concluded that the simplified method for estimating platelet AII receptor number is inaccurate and caution is urged in its use as a screening test for PIH.
Asunto(s)
Plaquetas/química , Hipertensión/diagnóstico , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Receptores de Angiotensina/análisis , Adulto , Femenino , Humanos , Embarazo , Complicaciones Cardiovasculares del Embarazo/sangre , Ensayo de Unión RadioliganteRESUMEN
OBJECTIVE: The relation between plasma angiotensin II concentrations and the platelet angiotensin II receptor was examined in four different groups of subjects. Platelet receptors were used as representative of physiologically significant sites such as in vascular smooth muscle. SUBJECTS: A control group consisting of non-pregnant females was studied together with three pregnant groups: normal pregnant women in both early and then late gestation and women with diagnosed pregnancy-induced hypertension (PIH). METHODS: Blood was collected from each subject for estimation of plasma angiotensin II concentration and isolation of platelets, which were then used in non-competitive binding studies. Both receptor capacity and affinity for the ligand were calculated for each subject. RESULTS: In the control group, a significant negative correlation between angiotensin II and receptor capacity was established. This was in marked contrast to the first trimester group which showed no such correlation and where there was a significant reduction or nil receptor capacity but only a slight elevation in mean plasma angiotensin II concentration. This phenomenon of reduced or absent binding persisted into the third trimester when plasma angiotensin II was significantly elevated compared with all other groups. PIH subjects had the lowest plasma angiotensin levels and 90% had clearly measurable binding to the platelet receptor, which was not however as high as that in the control group. Two normotensive subjects who demonstrated significant potentiation of receptor binding in the third trimester subsequently developed PIH. CONCLUSIONS: The inverse relation between plasma angiotensin II and its platelet receptor, found in non-pregnant subjects, is significantly altered in normal pregnancy. Reduced receptor capacity and lack of relation with circulating ligand observed in early gestation reflects an alteration at the receptor level which is independent of plasma angiotensin II concentration. This alteration appears to persist throughout pregnancy except in subjects predisposed to PIH when receptor binding is closer to non-pregnant values. Changes in receptor binding found in people who ultimately developed PIH but who were still clinically normal at the time suggest that binding to the platelet receptor could be used as a screening test for all primiparae to identify those predisposed to PIH later on in pregnancy.
Asunto(s)
Angiotensina II/sangre , Plaquetas/química , Hipertensión/sangre , Complicaciones Cardiovasculares del Embarazo/sangre , Receptores de Angiotensina/análisis , Adulto , Angiotensina II/metabolismo , Femenino , Humanos , Hipertensión/epidemiología , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Ensayo de Unión Radioligante , Receptores de Angiotensina/metabolismo , Factores de RiesgoRESUMEN
The expression of the glomerular receptor for angiotensin II (Ang II-R) was examined longitudinally following the induction of anti-glomerular basement membrane (GBM) nephritis in the rat. The specific aim of the project was to determine whether immunologically-induced glomerular injury led to significant abnormalities of the relationship between glomerular Ang II-R and its circulating ligand, Ang II. Scatchard analysis was used to measure Ang II-R on purified glomeruli at selected time intervals over two months following a single dose of sheep anti-rat GBM antibody. Corresponding values for plasma Ang II were determined. Receptor density fell to approximately 50% by 16 hours following the injection of antibody (control 96.4 +/- 9.3 x 10(6); nephritic 52.6 +/- 5.6 x 10(6) receptors/glomerulus; P less than 0.001) and there was a corresponding threefold increase in plasma Ang II (control 21.0 +/- 2.5; nephritic 66.6 +/- 20.6 pg/ml; P less than 0.01). However, this reduction in receptor binding could not be explained by the rise in plasma Ang II concentration, as effective blockade of the RAS by enalapril did not alter receptor expression (56.1 +/- 4.6 x 10(6) receptors/glomerulus). Subsequently, a rise in receptor density and a corresponding fall in plasma Ang II were observed: three days after antibody administration, receptor concentration had increased significantly above control values (150.5 +/- 11.9 x 10(6] while plasma Ang II was undetectable (that is, less than 5 pg/ml). Ang II-R remained elevated for the next two weeks but returned to normal four to eight weeks after the administration of nephrotoxic antibody.(ABSTRACT TRUNCATED AT 250 WORDS)