Effects of Systolic Blood Pressure on Brain Integrity in Multiple Sclerosis.

Background: In MS patients, hypertension is associated with a delayed diagnosis and an increased risk of progression. Understanding the mechanisms of this association could potentially lead to improved prevention of disease progression. We aimed to establish whether high blood pressure contributes to white-matter injury and brain atrophy in MS. Methods: Cross-sectional study of 95 patients with RRMS. Estimates of fractional anisotropy, gray-matter volume and lesion load were obtained from 3T MRI. We used fractional anisotropy voxel-based statistics to establish the effect of blood pressure on white matter tracts. Additionally, we used voxel-based morphometry (VBM) to study the effect on gray matter integrity. Results: Only 29.5% had normal blood pressure levels, with 52.6% suffering from prehypertension and 17.9% with hypertension. Increasing systolic blood pressure was associated with damage to posterior white-matter tracts as well as greater levels of gray matter atrophy, in particular in the frontal cortex. Age-adjusted linear regression indicated that neither lesion volume (ß = 0.002, 95%CI: 0.02-0.02; p = 0.85) or lesion number (ß = -0.004, 95%CI: 0.03-0.02; p = 0.74) were associated with systolic blood pressure. Conclusions: Prehypertension and hypertension are frequent in MS. Increased blood pressure is related to white- and gray-matter integrity, both related to MS disability outcomes. These findings suggest attention to the control of blood pressure in MS patients.

Volumetría hipocampal: análisis comparativo de los métodos de evaluación en enfermedad de Alzheimer / Hippocampal Volumetry: Comparative Analysis of Evaluation Methods in Alzheimer's Disease

Objetivo La atrofia hipocampal es uno de los biomarcadores radiológicos más sensibles de la enfermedad de Alzheimer (EA) y existen diferentes métodos para evaluarla: análisis subjetivo visual (ASV), análisis objetivo manual (AOM) y análisis objetivo automático (AOA). Nos proponemos comparar esos métodos, y evaluar si el AOA presenta una confiabilidad cercana al AOM (método de referencia) y superior al ASV. Materiales y Métodos Se seleccionaron retrospectivamente imágenes de resonancia magnética (RM) fast spoiled gradient-echo (FSPGR) de 28 sujetos (14 con deterioro cognitivo leve, 7 con EAy 7 controles). El ASV fue realizado por 10 radiólogos, clasificando la atrofia hipocampal en: nula, leve, moderada o severa. El AOM se basó en la segmentación manual de los hipocampos por dos operadores. El AOA fue realizada por medio del software FreeSurfer 5.3. Se calcularon coeficientes de correlación rho de Spearman para las variables discretas y coeficientes de correlación intraclase para las variables continuas. Resultados Los coeficientes de correlación entre los dos operadores que realizaron el AOM fueron de 0,88 (p < 0,0001) para los hipocampos izquierdos y de 0,86 (p < 0,0001) para los hipocampos derechos. El coeficiente de correlación entre todos los ASV (promediados) y AOM fue de-0,81 (IC 95%-0,96- -0,66). Los coeficientes de correlación entre el AOA y el AOM fue de 0,54 (p < 0,0001) para los hipocampos izquierdos y de 0,61 (p < 0,0001) para los hipocampos derechos. Conclusión Si bien el AOA tiene moderada correlación con el método de referencia, no es superior al ASV promedio y se deberían tomar recaudos antes de ser implementado en la práctica asistencial.

Objective Hippocampal atrophy is one of the most sensible radiological biomarkers of Alzheimer's disease. There are different methods to evaluate atrophy: visual subjective analysis (VSA), manual objective analysis (MOA) and automatic objective analysis (AOA). We will compare these methods and evaluate if AOA has a confidence similar to MOA (gold standard), and better than VSA. Materials and Methods We retrospectively selected 3D FSPGR MRI from 28 subjects of whom 14 had mild cognitive impairment, 7 Alzheimer's disease and 7 controls. VSA was performed by 10 radiologists who classified hippocampal atrophy in none, mild, moderate and severe. ForMOA, two operatorsmanually segmented both hippocampus from all subjects. AOA was performed by FreeSurfer 5.3. Spearman's rho correlation coefficient was calculated for discrete variables and intraclass correlation coefficient was calculated for continuous variables. Results Correlation coefficients between the operators that performed MOA was 0.88 (p < 0.0001) for left hippocampi and 0.86 (p < 0,0001) for right hippocampi. Correlation coefficients between mean VSA and MOA was-0,81 (95% CI-0,96- -0,66). Correlation coefficients between AOA and AOM was 0.54 (p < 0.0001) for left hippocampi and 0.61 (p < 0.0001) for right hippocampi. Conclusion Even though AOA has moderate correlation with the gold standard it is not superior to average VSA and should be implemented with care in clinical practice.

Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): neuropsychological evolution profile after one-year follow up.

The Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI) study is a longitudinal prospective cohort of 50 participants at a single institution in Buenos Aires, Argentina. Longitudinal assessments on a neuropsychological test battery were performed on 15 controls, 24 mild cognitive impairment (MCI) patients and 12 Alzheimer's disease (AD) dementia patients. In our study population, there was a high prevalence of positive AD biomarkers in the AD group, 92.3% (12/13); and a low prevalence in the normal controls, 20%; almost half (48%) of the patients diagnosed with MCI had positive amyloid detection. After a one year, the significant differences found at baseline on neuropsychological testing were similar at the follow-up assessment even though the AD group had significantly altered its functional performance (FAQ and CDR). The exception was semantic fluency, which showed greater impairment between the AD group and MCI and normal controls respectively. For these tests, the addition of AD biomarkers as a variable did not significantly alter the variations previously found for the established clinical group's model. Finally, the one-year conversion rate to dementia was 20% in the MCI cohort.

Frontal sinus ontogeny and covariation with bone structures in a modern human population.

In humans, the frontal sinus (FS) is located in the medial part of the supraorbital region, sometimes expanded throughout the frontal squama. It exhibits high morphological variability, but its general form appears to be constrained by surrounding structures. The goal of this study is to analyze FS growth and test for covariation between FS volume and the glabellar region, upper nasal region, bone thickness and endocranial size in a human sample from Argentina. The sample comprises 149 reconstructions derived from computed tomography images of individuals aged 0-31 years. Volume of the FS and measurements of the surrounding structures were recorded. The FS growth trajectory was assessed by parametric and nonparametric methods, and covariation was determined using correlations and partial correlations. The FS volume could be measured at an age of about 6 years and older; adults had no aplasia but hyperplasia was found in some cases. Since the most conspicuous characteristic found was variation among individuals, the nonparametric smoothing spline produced very poor fitting. The modified logistic function was the only parametric method providing significant parameters. Sexes differed in the age at which FS growth began and ended, with FS developing earlier but at a slower rate in females than in males. The FS volume did not correlate with either upper nasal width or endocranial volume, but it correlated with bone thickness measurements (mainly from the glabellar region), even when age was held constant. Expansion of the FS at the frontal poles also correlated with frontal bone thickness. Despite the difficulty in modeling and predicting the trajectory and morphology of FS, our results suggest that it is affected by its surrounding bony environment.

Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): neuropsychological evolution profile after one-year follow up / Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI): evolução do perfil neuropsicológico depois de um ano de seguimento

ABSTRACT The Argentina-Alzheimer's disease neuroimaging initiative (Arg-ADNI) study is a longitudinal prospective cohort of 50 participants at a single institution in Buenos Aires, Argentina. Longitudinal assessments on a neuropsychological test battery were performed on 15 controls, 24 mild cognitive impairment (MCI) patients and 12 Alzheimer's disease (AD) dementia patients. In our study population, there was a high prevalence of positive AD biomarkers in the AD group, 92.3% (12/13); and a low prevalence in the normal controls, 20%; almost half (48%) of the patients diagnosed with MCI had positive amyloid detection. After a one year, the significant differences found at baseline on neuropsychological testing were similar at the follow-up assessment even though the AD group had significantly altered its functional performance (FAQ and CDR). The exception was semantic fluency, which showed greater impairment between the AD group and MCI and normal controls respectively. For these tests, the addition of AD biomarkers as a variable did not significantly alter the variations previously found for the established clinical group's model. Finally, the one-year conversion rate to dementia was 20% in the MCI cohort.

RESUMO El estudio de Argentina-Alzheimer's Disease Neuroimaging Initiative (Arg-ADNI) es una cohorte prospectiva de 50 pacientes seguidos en una misma institución. Fueron evaluados cognitivamente 15 controles normales (CN), 24 sujetos con deterioro cognitivo leve (DCL) y 12 con demencia tipo Alzheimer (DTA) leve. En los DTA, 92,3% tuvieron biomarcadores positivos para Alzheimer y 20% en los CN. Casi la mitad de los DCL presentaron biomarcadores positivos. Después de un año de seguimiento, la diferencias significativas halladas en la visita de inicio en las pruebas cognitivas fueron similares al año aunque los DTA tuvieron empeoramiento funcional medido en el FAQ y CDR. La excepción fue la fluencia semántica, la cual mostró mayor declinación entre DTA y los demás grupos. La incorporación de los biomarcadores como variable no alteró significativamente los hallazgos de grupo. La tasa de conversión a demencia anual fue del 20%.

Morphological Integration of the Orbital Region in a Human Ontogenetic Sample.

Most studies on craniofacial morphology have focused on adult individuals, but patterns of variation are the outcome of genetic and epigenetic variables that interact throughout ontogeny. Among cranial regions, the orbits exhibit morphological variation and occupy an intermediate position between neurocranial and facial structures. The main objective of this work was to analyze postnatal ontogenetic variation and covariation in the morphology of the orbital region in a cross-sectional series of humans from 0 to 31 years old. Landmarks and semilandmarks were digitized on the orbital rim, as well as in neighboring neural and facial structures. Data were analyzed using geometric morphometrics. Results indicated that orbital size increases during the first years of postnatal life, while the shape of the orbital aperture does not change significantly with age. In general, the pattern and magnitude of shape covariation do not vary markedly during postnatal life although some subtle shifts were documented. Additionally, the shape of the orbital aperture is more related to the anterior neurocranium than to zygomatic structures, even when the allometry is adjusted. Although we expected some influence from postnatal craniofacial growth and from some functional factors, such as mastication, on the development of the orbits, this assumption was not completely supported by our results. As a whole, our findings are in line with the prediction of an early influence of the eyes and extraocular tissues on orbital morphology, and could be interpreted in relation to processes promoting early neural development that coordinately affects orbital traits and the neurocranial skeleton.

Ontogenetic changes in cranial vault thickness in a modern sample of Homo sapiens.

OBJECTIVES: This work assesses cranial vault thickness (CVT) ontogenetic changes using a computed tomography database to register thickness across multiple regions. METHODS: Vault images of 143 individuals from 0 to 31 years old were analyzed by thickness semiautomatic measurements. For each individual, we obtained a thickness mean measure (TMM) and its coefficient of variation, a measure of endocranial volume (EV), the distribution of relative frequencies of thickness-relative frequency polygon, and a topographic mapping that shows the thickness arrangement through a chromatic scale. Ontogenetic changes of these variables were evaluated by different regression models (TMM vs. age, EV vs. age, TMM vs. EV) and visual comparisons between the age groups. RESULTS: TMM increased during ontogeny until the onset of adulthood without sex differences, but the most accelerated growth rates occur during the first 6 years of postnatal life. TMM variations were associated with EV only in infants and children, but not in later periods. The polygons showed a flattening during ontogeny, probably due to an increase in thickness variation within individuals. However, the adult pattern of thickness arrangement, with the lateral region thinner than the regions near sagittal plane, was detected from infancy. CONCLUSION: The pattern of thickness arrangement is established early in ontogeny but CVT increases and changes in distribution until adolescence. Several factors may influence CVT, such as the brain, muscles, vessels, and sutures.

Ontogenetic patterns of morphological variation in the ectocranial human vault.

The skull is considered a modular structure in which different parts are influenced by different factors and, as a result, achieve adult shape at different ages. Previous studies have suggested that the basicranium presents a modular pattern that distinguishes sagittal and lateral parts, probably affected by the brain and masticatory structures, respectively. The vault of modern humans, in contrast, has been considered as a highly integrated system mainly influenced by brain growth. Here, we explored developmental shape variation in sagittal and lateral ectocranial vault in humans in order to assess if both regions are ontogenetically dissociated. We used a sample of 135 cranial computed tomography images from 0 to 31 ages. Landmarks and semilandmarks were collected on sagittal and lateral regions and geometric morphometric techniques were applied separately for each region. On the shape coordinates, we used Goodall's F-test in order to assess the age when the adult configuration is attained. Principal component analysis enabled us to evaluate shape variation during ontogeny. Results indicated that both sagittal and lateral structures attain adult shape at early adolescence. Both regions express coordinated shape modifications probably due to shared developmental factors. It is concluded that masticatory muscles may not exert a strong enough influence to produce independent variation in the lateral traits. Thus, it is likely that the brain integrates sagittal and lateral parts of the vault across human ontogeny.

Measurement error of 3D cranial landmarks of an ontogenetic sample using Computed Tomography.

BACKGROUND/AIM: Computed Tomography (CT) is a powerful tool in craniofacial research that focuses on morphological variation. In this field, an ontogenetic approach has been taken to study the developmental sources of variation and to understand the basis of morphological evolution. This work aimed to determine measurement error (ME) in cranial CT in diverse developmental stages and to characterize how this error relates to different types of landmarks. MATERIAL AND METHODS: We used a sample of fifteen skulls ranging from 0 to 31 years. Two observers placed landmarks in each image three times. Measurement error was assessed before and after Generalized Procrustes Analysis. RESULTS: The results indicated that ME is larger in neurocranial structures, which are described mainly by type III landmarks and semilandmarks. In addition, adult and infant specimens showed the same level of ME. These results are specially relevant in the context of craniofacial growth research. CONCLUSION: CT images have become a frequent evidence to study cranial variation. Evaluation of ME gives insight into the potential source of error in interpreting results. Neural structures present higher ME which is mainly associated to landmark localization. However, this error is irrespective of age. If landmarks are correctly selected, they can be analyzed with the same level of reliability in adults and subadults.

Allometries throughout the late prenatal and early postnatal human craniofacial ontogeny.

Craniofacial shape changes throughout the late prenatal and early postnatal ontogeny (32-47 weeks of gestational age) were explored. The purpose was to evaluate whether the skull follows an allometric growth pattern, as was observed in other ontogenetic periods, and to assess shape variation patterns for the cranial vault, cranial base, and face. Thirty three-dimensional landmarks were registered in 54 skulls. Wire-frames were built with landmarks to observe shape variation in the following cranial components: anteroneural, midneural, posteroneural, optic, respiratory, masticatory, and alveolar. The landmark configurations were subjected to generalized Procrustes analyses, and the shape coordinates obtained were subjected to Principal Components Analyses. Multivariate regression of the shape variables (the principal components) on the size vector (the centroid size) was performed to assess allometries. Transformation grids were constructed to identify how cranial components interact across ontogeny. Results indicated that highly significant shape changes depend on size changes. Important shape variation in the vault, small variation in the cranial base, and no variation in the face were observed. Brain growth is proposed to be the major influence on craniofacial shape change, which produces a relative elongation and compression of midneural and posteroneural components. The cranial base elongates by intrinsic factors and affects position of the face. Ontogenetically, the cranial base seems to be independent with respect to brain growth, in contrast to what has been suggested in comparisons at higher taxonomic levels.