Impairment of visuospatial/visuoconstructional skills in multiple sclerosis patients: the correlation with regional lesion load and subcortical atrophy

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Marasescu, M. Cerezo Garcia, Y. Aladro Benito" "autores" => array:3 [ 0 => array:4 [ "nombre" => "R." "apellidos" => "Marasescu" "email" => array:1 [ 0 => "raluca_marasescu@yahoo.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "M." "apellidos" => "Cerezo Garcia" ] 2 => array:2 [ "nombre" => "Y." "apellidos" => "Aladro Benito" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neurología, Hospital Universitario de Getafe, Getafe, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Afectación visuoespacial/visuoconstrucción en pacientes con esclerosis múltiple. Relación con el volumen lesional regional y la atrofia subcortical" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1057 "Ancho" => 1800 "Tamanyo" => 139779 ] ] "descripcion" => array:1 [ "en" => "Lesions are manually marked and their area is automatically calculated by software specific for irregular areas. Total LV is calculated by adding the area of all lesions and multiplying the result by slice thickness." ] ] ] "textoCompleto" => "IntroductionCognitive losses develop in 40%-65% of patients with multiple sclerosis (MS) over the course of the disease. The most frequently affected areas are information processing speed (IPS), attention, memory, and executive functions.<a class="elsevierStyleCrossRefs" href="#bib0195">1–7</a> Unlike physical symptoms, cognitive impairment (CI) does not usually remit. CI is more frequent in late stages of the disease but may cause disability during the early stages of relapsing-remitting MS.<a class="elsevierStyleCrossRefs" href="#bib0220">6,8,9</a>Most studies found a weak, inconsistent correlation between CI in MS and lesion volume (LV) in white matter (WM) measured using T2 and T1-weighted sequences.<a class="elsevierStyleCrossRef" href="#bib0240">10</a> Measurements of global and regional cerebral atrophy are consistently related with CI, specifically in case of grey matter atrophy.<a class="elsevierStyleCrossRefs" href="#bib0245">11–13</a> Specific cognitive domain studies using LV and regional atrophy of the corresponding brain regions are heterogeneous and focus particularly on IPS, memory, and executive function.<a class="elsevierStyleCrossRefs" href="#bib0250">12,14–19</a>Although WM lesions of parietal-temporal-occipital areas are frequent in MS, deficits of visuospatial (VS) and visuoconstructive (VC) functions, which were observed in approximately 25% of the patients, have rarely been studied.<a class="elsevierStyleCrossRefs" href="#bib0205">3,7,20</a> VS dysfunction translates into a deficit in the representation and integration of images, and spatial localisation and object tracking. VC dysfunction leads to difficulties with spatial organisation of visual information, and to problems with assembly and drawing. Both functions require visual processing pathways to be intact: occipitoparietal or dorsal stream pathways (also known as magnocellular), responsible for movement analysis and visuomotor coordination; inferior occipitotemporal or ventral stream pathway (parvocellular) related to object perception (shape and colour); and the medial superior temporal area, important for VS functions.<a class="elsevierStyleCrossRefs" href="#bib0295">21,22</a>We have assessed the relationship between impairment of VS and VC skills and LV on the parietal-temporal-occipital association area and cortical brain atrophy in MS patients. LV was measured manually and the total area was later calculated automatically; brain atrophy was estimated with linear measurements.MethodsWe selected 21 MS patients (2010 McDonald criteria) with VS and VC impairment, and 13 without CI (control group) out of a total of 100 MS patients. All of these patients underwent routine and comprehensive neuropsychological assessment including IPS, memory, learning, attention, executive functions, language processing, and VS and VC skills. We excluded patients with psychiatric disorders, those under treatment with psychotropic drugs, and patients with any visual impairment and/or alteration of eye movements mentioned in their medical records, due to the potential for interference with performance on cognitive tests.We recorded age, sex, type of MS, degree of disability measured by the Expanded Disability Status Scale (EDSS), and MS progression time when the neuropsychological evaluation took place. Level of education reported as years of schooling was also included.Levels of depression (Beck Depression Inventory) and anxiety (State-Trait Anxiety Inventory) were analysed to control for their effect on cognitive performance.Measurement instrumentsVS and VC skills were evaluated using the block design test (BDT) and the picture completion test (PCT) of the Wechsler Adult Intelligence Scale (WAIS-III), and the Rey–Osterrieth Complex Figure Test (ROCF): copy accuracy and immediate reproduction.BDTThe patient recreates geometric designs using blocks. This assesses the capacity to analyse and synthesise abstract geometrical drawings, problem solution strategies, psychomotor integration, speed, and distraction. Scaled scores of ≤7 (≤−1 SD) are considered abnormal.PCTPatients are provided with pictures of everyday objects with a part missing that they attempt to identify. This is a time-dependent test that assesses the capacity to visually organise objects. Scaled scores of ≤7 (≤−1 SD) are considered abnormal.Rey–Osterrieth complex figureThis test analyses perceptual organisation and visual memory by asking the patient to reproduce a figure after an interference period. It assesses the capacity to organise and plan strategies to resolve problems, as well as VC skills. Percentiles ≤30 indicate pathology due to the ceiling effect of this test (most of the subjects obtain high scores at the upper part of the distribution).Obtaining abnormal results in at least one test signified a VS and/or VC skills deficit.Measuring LV using magnetic resonanceA brain MRI was conducted (Siemens, 1.5Tesla). The MRI consisted of 5mm slices of axial T1-weighted sequences and coronal Fluid-Attenuated Inversion Recovery (FLAIR) sequences, which were used to identify and measure WM lesions. WM LV was quantified in the parietal-temporal-occipital association area located between the postcentral and occipital sulci. A researcher blinded to the results of the neuropsychological tests drew the lesion borders. The area of each lesion was automatically calculated by the software that processes the MRI scans (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). WM LV of the region is calculated by adding the area of all lesions in all slices and multiplying the result by the slice thickness. Linear measurements of brain atrophy are also conducted using the third ventricle width (TVW) and bicaudate ratio (BCR)<a class="elsevierStyleCrossRefs" href="#bib0305">23–25</a> derived from FLAIR sequences. Time elapsed between the neuropsychological examination and the MRI was no longer than 3 months in any case.<elsevierMultimedia ident="fig0005"></elsevierMultimedia>Statistical analysisWe used SPSS software version 18.0. We performed descriptive and frequency analyses for both groups. We used the chi-square test (categorical variables) for calculating the inter-group comparison (study group and control group), and the t-test (continuous variables) for independent samples.We analysed the relationship between VS–VC tasks and clinical and radiological variables in each MS patient, with or without CI. To do this, we used bivariate and partial correlations, and controlled for age and years of schooling (Spearman rank). We also used a linear regression model (stepwise method) employing each of the 3 cognitive tests as dependent variables, while demographic and clinical variables and MRI measurements (LV on T1-weighted images of the right, left, and both hemispheres, and FLAIR LV images of the right, left, and both hemispheres, TVW, and BCR) which showed a statistically significant relationship in the bivariate analysis were used as independent variables. Age, sex, and years of schooling were always included in the model.Results<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> includes the clinical and radiological characteristics of the 2 groups of MS patients. We observed statistically significant differences between the control group (MS patients without CI) and the group of MS patients with impaired VS and VC skills regarding years of schooling, EDSS score, type of MS, and all LV and subcortical atrophy MRI measurements (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>CorrelationsWe obtained no significant correlations between cognitive tests and sex, type of MS, or time of progression of MS. Degree of depression (Beck Depression Inventory: PCT, P=.081; BDT, P=.106; ROCF P=.933), and anxiety (State-Trait Anxiety Inventory: PCT, P=.142; BDT, P=.134; ROCF, P=.126) were not correlated with performance on the tests.Education level significantly influenced the score on the 3 tests (PCT, P=.010; BDT, P=.005; ROCF, P=.014) though age only influenced results on the ROCF test (P=.005). Therefore, their effect is controlled in the bivariate correlations (EDSS score and MRI measurements).<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the variables which are significantly related to performance regarding VS–VC tasks. Of special note is the strong inverse correlation with all LV and atrophy MRI measurements (P<.01) which remains after controlling for age and years of schooling, except in the case of the PCT and central atrophy measurements. FLAIR derived LV of the left and both hemispheres shows a stronger and more uniform correlation with the 3 tests than other volume measurements. However, the most marked association is seen between TVW and VC skills (BDT and ROCF-copy accuracy, r=0.548/P=.001 and r=.608/P<.000, respectively) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Linear regressionNo clinical variable is able to explain performance on cognitive tests, but years of schooling and age can explain VC performance (ROCF). Additionally, TVW has an independent and statistically significant influence on VC performance (BDT and ROCF). We further observed an independent statistically significant effect of the regional FLAIR LV on VS tasks (PCT), with a lower impact (considerable LV increases were required to notably modify test scores). The remaining radiological variables do not show any statistically significant relationship (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>DiscussionImpaired VS and VC skills were detected in 20%-26%<a class="elsevierStyleCrossRefs" href="#bib0205">3,7,20</a> of the MS patients. This low percentage is surprising due to the observation, on most of the patients’ MRI scans, of extensive WM involvement in the parieto-occipital and temporal-occipital areas, the precise regions involved in these functions.<a class="elsevierStyleCrossRefs" href="#bib0295">21,22</a> Several explanations can be put forward: the tests used to routinely study CI in MS might have low sensitivity to impairment of these functions, or alternatively, these functions might require activation of low brain volume, or are replaced by the extensive connections in these areas. In this article, we studied these functions with tests which are not routinely used for CI evaluation in MS. However, these tests are specific and largely standardised and validated for the analysis of these functions in a number of countries. BDT and PCT (WAIS III subtests), and ROCF are well known tools that analyse complex visual perception and organisation tasks, in addition to visuomotor and VC tasks. Although this is a retrospective study with its associated weak points (which we will analyse later), its interest resides in the specific analysis of these functions and their relationship with structural changes in the brain areas involved in these tasks. This approach has been only sporadically addressed in the literature (as searched on MedLine).<a class="elsevierStyleCrossRefs" href="#bib0305">23,26,27</a>In our study, we have observed VS and VC task impairment in 21% of the patients. We are likely underestimating the true prevalence of impairment, since we have excluded patients with any mention of even minimal symptoms or signs of visual impairment or ocular motility in their medical records in order to avoid bias when interpreting the results. Vleugels et al. found VS impairment in 26% of the 49 patients studied with an extensive battery of tests specific to these skills.<a class="elsevierStyleCrossRef" href="#bib0290">20</a> This is the highest frequency so far reported.Our VS impaired MS patients have significantly higher EDSS scores, more WM LV in the parietal-temporal-occipital association area, and greater subcortical atrophy than MS patients with no CI at all.Many other authors have described the association between CI and EDSS scores,<a class="elsevierStyleCrossRefs" href="#bib0225">7,8,11,24</a> although it is a well-known fact that patients with little motor dysfunction can show substantial CI<a class="elsevierStyleCrossRefs" href="#bib0250">12,20</a> and that some domains such as IPS may be altered before motor function.<a class="elsevierStyleCrossRef" href="#bib0220">6</a>We observed a significant inverse association between performance on the 3 tests (PCT, BDT, and ROCF) and all MRI measurements. Regional FLAIR LV images showed a stronger correlation with all tests than T1-weighted sequence LV measurements, while at the same time maintaining independent significance on multivariate analysis with regards to VS tasks, although to a lesser extent. T1-weighted LV images are better at revealing axonal damage, which is not surprising since FLAIR sequences enable better identification of lesions and are more sensitive to periventricular and grey matter-WM interface lesions.<a class="elsevierStyleCrossRefs" href="#bib0330">28,29</a> Correlations between T1 and T2-weighted LV images and CI have been only moderately and inconsistently mentioned in the medical literature.<a class="elsevierStyleCrossRefs" href="#bib0325">27,30,31</a> In contrast to our study, Lazeron et al.<a class="elsevierStyleCrossRef" href="#bib0310">24</a> did not find a correlation between VS processing and regional LV in a sample of 32 patients studied with an extensive battery which included only one VS processing test. These results might be explained, at least in part, by differences among patients (their patients were older and had higher EDSS scores) and the test used (they used a VS task with a significant VS memory load and did not assess VS skills). This moderate and inconsistent correlation between LV and CI is partially explained by problems inherent to the measurement itself: areas of inflammation, oedema, and gliosis are included in the assessment of volume, which masks some WM atrophy; cortical plaques are difficult to detect by conventional MRI and so are usually not included in the analysis,<a class="elsevierStyleCrossRef" href="#bib0350">32</a> and structural changes in normal-appearing WM, with subsequent alteration in connectivity to cortical areas, as has been demonstrated by anisotropy studies.<a class="elsevierStyleCrossRefs" href="#bib0345">31,33</a>Although both methods of brain atrophy evaluation (BCR and TVW) show a strong correlation with VS and VC impairment in 2 out of the 3 tests (BDT, P=.004 and .001; ROCF, P=.004 and .000), only TVW explains the variations in VC task results, with a higher impact which is independent of education level. By using the same indirect measurements, other authors have observed a close association between subcortical atrophy and cognitive dysfunction.<a class="elsevierStyleCrossRefs" href="#bib0305">23,28,34,35</a> However, only Benedict et al. assess VS memory using the Brief Visuospatial Memory Test-Revised; VC skills were not assessed.<a class="elsevierStyleCrossRef" href="#bib0305">23</a> Increased BCR is related to extensive frontal WM atrophy while elevated TVW is associated with the volume of the thalamus, a structure with extensive cortical connections. To perform complex activities which involve organisation and praxis functions linked to frontal brain areas, such as VC tasks, this connectivity is hypothetically necessary. The thalamus appears to be one of the brain regions with a higher prevalence of atrophy during the initial stages of MS. It is also strongly correlated with physical and cognitive disability<a class="elsevierStyleCrossRefs" href="#bib0370">36,37</a> and is a good marker of poor outcome.<a class="elsevierStyleCrossRef" href="#bib0380">38</a> Finally, although both measurements (BCR and TVW) show an appreciable intra- and interobserver variability which depends on slice thickness, they have demonstrated their usefulness in monitoring brain atrophy progression in comparison with SIENAX, an automatic method for estimating brain volume which is widely used for cases of MS.<a class="elsevierStyleCrossRef" href="#bib0315">25</a>Our study does have some limitations. For one thing, it is a retrospective study with a small patient sample. To minimise unavoidable variability in the acquisition of MR images, a single researcher blinded to clinical and neuropsychological parameters performed all the LV and atrophy measurements. Also, the study area was previously established using fixed coordinates. The same neuropsychologist evaluated all the patients in order to avoid biases in test administration. Another study weakness is the effect of varying education levels in groups of MS patients with or without CI, which is minimised in the data analysis adjusted for this parameter.In conclusion, our study analyses specific cognitive domains, VC and VS tasks, and their relationship with WM LV in parietal-temporal-occipital association areas, and subcortical brain atrophy. FLAIR LV and subcortical atrophy show a strong correlation with cognitive performance in these domains. Subcortical atrophy, estimated from TVW which measures thalamic atrophy, is highly correlated with VC task impairment, while regional LV is highly correlated with VS task impairment. These results point to the need to extend the study and use automated LV measurements in a larger sample.Conflicts of interestThe authors declare no conflicts of interest.Marta Cerezo Gracia has been awarded a grant by Merck Serono and BioGen for the application of neuropsychological tests." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres627202" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methodology" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec640288" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres627203" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Metodología" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec640289" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Measurement instruments" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "BDT" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "PCT" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Rey–Osterrieth complex figure" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Measuring LV using magnetic resonance" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Statistical analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Correlations" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Linear regression" ] ] ] 7 => array:2 [ "identificador" => "sec0060" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflicts of interest" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-02-22" "fechaAceptado" => "2015-06-04" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec640288" "palabras" => array:5 [ 0 => "Multiple sclerosis" 1 => "Lesion volume" 2 => "Cognitive impairment" 3 => "Subcortical atrophy" 4 => "Visuospatial/visuoconstructional skills" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec640289" "palabras" => array:5 [ 0 => "Esclerosis múltiple" 1 => "Volumen lesional" 2 => "Déficits cognitivos" 3 => "Atrofia sucortical" 4 => "Habilidades visuoespaciales/visuoconstructivas" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionAbout 20% to 26% of patients with multiple sclerosis (MS) show alterations in visuospatial/visuoconstructive (VS–VC) skills even though temporo-parieto-occipital impairment is a frequent finding in magnetic resonance imaging. No studies have specifically analysed the relationship between these functions and lesion volume (LV) in these specific brain areas. ObjectiveTo evaluate the relationship between VS–VC impairment and magnetic resonance imaging temporo-parieto-occipital LV with subcortical atrophy in patients with MS. MethodologyOf 100 MS patients undergoing a routine neuropsychological evaluation, 21 were selected because they displayed VS–VC impairments in the following tests: incomplete picture, block design (WAIS-III), and Rey–Osterrieth Complex Figure Test. We also selected 13 MS patients without cognitive impairment (control group). Regional LV was measured in FLAIR and T1-weighted images using a semiautomated method; subcortical atrophy was measured by bicaudate ratio and third ventricle width. Partial correlations (controlling for age and years of schooling) and linear regression analysis were employed to analyse correlations between magnetic resonance imaging parameters and cognitive performance. ResultsAll measures of LV and brain atrophy were significantly higher in patients with cognitive impairment. Regional LV, bicaudate ratio, and third ventricle width are significantly and inversely correlated with cognitive performance; the strongest correlation was between third ventricle width and VC performance (block design: P=.001; Rey–Osterrieth complex figure: P<.000). In the multivariate analysis, third ventricle width only had a significant effect on performance of VC tasks (block design: P=.000; Rey–Osterrieth complex figure: P=.000), and regional FLAIR VL was linked to the VS task (incomplete picture; P=.002). ConclusionsMeasures of subcortical atrophy explain the variations in performance on visuocostructive tasks, and regional FLAIR VL measures are linked to VS tasks." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Objective" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methodology" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónSolo el 20-26% de los pacientes con esclerosis múltiple presenta déficits en habilidades visuoespaciales-visuoconstructivas (VE-VC) pese a la frecuente afectación témporo-parieto-occipital en resonancia magnética. No hay estudios que analicen la relación entre estas funciones y el volumen lesional (VL) de estas áreas cerebrales. ObjetivoEvaluar la relación del VL parieto-occipito-temporal y la atrofia subcortical con el rendimiento en funciones VE-VC en esclerosis múltiple. MetodologíaDe 100 pacientes de esclerosis múltiple con evaluación neuropsicológica rutinaria se seleccionan 21 por afectación en habilidades VE-VC, medidas por Figuras incompletas, Cubos (WAIS-III) y Figura compleja de Rey-Osterrieth, y 13 sin déficit cognitivo (grupo control). El VL regional se cuantifica por un método semiautomático en secuencias FLAIR y T1, y la atrofia subcortical por el ratio bicaudado y la anchura del iii ventrículo (AIIIV). Se utilizan correlaciones parciales (controlando con edad y escolarización) y regresión lineal para analizar la relación entre los parámetros de resonancia magnética y el rendimiento cognitivo. ResultadosTodas las medidas de VL y de atrofia cerebral son significativamente mayores en pacientes con deterioro cognitivo. El VL regional en FLAIR, ratio bicaudado y AIIIV muestran significativa correlación inversa con el rendimiento cognitivo, mayor entre la AIIIV y VC (Cubos: p=0,001; Figura compleja de Rey-Osterrieth: p<0,000). En el análisis multivariante, la AIIIV influye significativamente en tareas de VC (Cubos: p=0,000; Figura compleja de Rey-Osterrieth: p=0,000) y el VL regional en FLAIR en tareas VE (Figuras incompletas; p=0,002). ConclusionesLas medidas de atrofia subcortical se relacionan con tareas de visuoconstrucción y el VL regional con tareas VE." "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Objetivo" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Metodología" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Resultados" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Marasescu R, Cerezo Garcia M, Aladro Benito Y. Afectación visuoespacial/visuoconstrucción en pacientes con esclerosis múltiple. Relación con el volumen lesional regional y la atrofia subcortical. Neurología. 2016;31:169–175." ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1057 "Ancho" => 1800 "Tamanyo" => 139779 ] ] "descripcion" => array:1 [ "en" => "Lesions are manually marked and their area is automatically calculated by software specific for irregular areas. Total LV is calculated by adding the area of all lesions and multiplying the result by slice thickness." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "TVW: third ventricle width; SD: standard deviation; EDSS: Kurtzke Expanded Disability Status Scale; FLAIR: Fluid-Attenuated Inversion Recovery; BVR: bivariate ratio; RR: relapsing-remitting; FLAIR LV: lesion volume on a FLAIR MRI sequence; T1 LV: lesion volume on a T1-weighted MRI sequence." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study group n=21 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group n=13 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P-value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">40.38±12.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">35±6.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.229 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex: women/men (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9/4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.891 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EDSS scores (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.09±1.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.19±1.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.002<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RR/progressive (n) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15/6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13/0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.034<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Years of schooling (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.43±2.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13±3.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.029<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Progression time in months (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">88.76±61.69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">77.69±52.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.582 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BVR \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.15±0.046 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.11±0.017 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.005<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TVW (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8±2.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.88±1.73 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.000<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FLAIR LV (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10,694.07±8575.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2548.61±3280.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1 LV (mm3) (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6008.95±6959.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">295.42±647.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.006<a class="elsevierStyleCrossRef" href="#tblfn0005">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1028941.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "Significance level≤.05." ] ] ] "descripcion" => array:1 [ "en" => "Clinical and radiological characteristics." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "EDSS: degree of disability according to the Expanded Disability Status Scale; FLAIR: Fluid-Attenuated Inversion Recovery; MRI: magnetic resonance imaging; T1 LV: lesion volume on a T1-weighted MRI sequence.Significance level≤.05." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables: Age, clinical variables, MRI Anxiety, depression \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Picture completion (r/P) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Block design (r/P) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rey–Osterrieth complex figure (i/P) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EDSS score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.506/.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.580/.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.560/.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on right axial T1-weighted image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.520/.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.444/.012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.389/.031 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on left axial T1-weighted image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.515/.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.445/.012 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.437/.014 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total LV on axial T1-weighted image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.523/.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.449/.011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.417/.019 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on right coronal FLAIR image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.515/.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.517/.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.456/.010 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on left coronal FLAIR image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.505/.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.504/.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.507/.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total LV on coronal FLAIR image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.524/.002 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.513/.003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.514/.003 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bicaudate ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.323/.077 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.500/.004 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.503/.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Third ventricle width (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.276/.133 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.548/.001 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.608/.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1028942.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Partial correlations between EDSS scores, LV on T1-weighted sequences, FLAIR; atrophy measurements and cognitive tests, adjusted for age and level of education." ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "EDSS: degree of disability according to the Expanded Disability Status Scale; FLAIR: Fluid-Attenuated Inversion Recovery; MRI: magnetic resonance imaging; VC: visuoconstructive; VS: visuospatial; T1 LV: lesion volume on a T1-weighted MRI sequence." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MRI measurements \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Figure completion (P) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Block design (P) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rey–Osterrieth complex figure (P) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on right axial T1-weighted image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.518 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.210 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.860 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on left axial T1-weighted image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.326 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.227 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.965 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total LV on axial T1-weighted image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.390 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.214 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.911 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on right coronal FLAIR image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.576 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.217 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.664 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on left coronal FLAIR image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.315 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.217 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.513 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total LV on coronal FLAIR image (mm3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.002<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.190 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.906 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bicaudate ratio \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.575 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.688 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.921 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Third ventricle width (mm) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.968 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.000<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.000<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.405 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.721 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.004<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.618 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.115 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.448 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Education (in years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.008<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.014<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.042<a class="elsevierStyleCrossRef" href="#tblfn0010">*</a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EDSS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.333 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−.207 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.199 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Progression timeline \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.488 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.333 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.689 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1028943.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "*" "nota" => "Significance level≤.05." ] ] ] "descripcion" => array:1 [ "en" => "Linear regression to evaluate the effect of MRI parameters on VS–VC tasks." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:38 [ 0 => array:3 [ "identificador" => "bib0195" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Risk factors for and management of cognitive dysfunction in multiple sclerosis" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "R.H. 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Afectación visuoespacial/visuoconstrucción en pacientes con esclerosis múltiple. Relación con el volumen lesional regional y la atrofia subcortical

R. Marasescu

Corresponding author

raluca_marasescu@yahoo.com

Corresponding author.

, M. Cerezo Garcia, Y. Aladro Benito

Servicio de Neurología, Hospital Universitario de Getafe, Getafe, Spain

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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Lesions are manually marked and their area is automatically calculated by software specific for irregular areas&#46; Total LV is calculated by adding the area of all lesions and multiplying the result by slice thickness&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Cognitive losses develop in 40&#37;-65&#37; of patients with multiple sclerosis &#40;MS&#41; over the course of the disease&#46; The most frequently affected areas are information processing speed &#40;IPS&#41;&#44; attention&#44; memory&#44; and executive functions&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">1&#8211;7</span></a> Unlike physical symptoms&#44; cognitive impairment &#40;CI&#41; does not usually remit&#46; CI is more frequent in late stages of the disease but may cause disability during the early stages of relapsing-remitting MS&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">6&#44;8&#44;9</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Most studies found a weak&#44; inconsistent correlation between CI in MS and lesion volume &#40;LV&#41; in white matter &#40;WM&#41; measured using T2 and T1-weighted sequences&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">10</span></a> Measurements of global and regional cerebral atrophy are consistently related with CI&#44; specifically in case of grey matter atrophy&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">11&#8211;13</span></a> Specific cognitive domain studies using LV and regional atrophy of the corresponding brain regions are heterogeneous and focus particularly on IPS&#44; memory&#44; and executive function&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">12&#44;14&#8211;19</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although WM lesions of parietal-temporal-occipital areas are frequent in MS&#44; deficits of visuospatial &#40;VS&#41; and visuoconstructive &#40;VC&#41; functions&#44; which were observed in approximately 25&#37; of the patients&#44; have rarely been studied&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">3&#44;7&#44;20</span></a> VS dysfunction translates into a deficit in the representation and integration of images&#44; and spatial localisation and object tracking&#46; VC dysfunction leads to difficulties with spatial organisation of visual information&#44; and to problems with assembly and drawing&#46; Both functions require visual processing pathways to be intact&#58; occipitoparietal or dorsal stream pathways &#40;also known as magnocellular&#41;&#44; responsible for movement analysis and visuomotor coordination&#59; inferior occipitotemporal or ventral stream pathway &#40;parvocellular&#41; related to object perception &#40;shape and colour&#41;&#59; and the medial superior temporal area&#44; important for VS functions&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">21&#44;22</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">We have assessed the relationship between impairment of VS and VC skills and LV on the parietal-temporal-occipital association area and cortical brain atrophy in MS patients&#46; LV was measured manually and the total area was later calculated automatically&#59; brain atrophy was estimated with linear measurements&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">We selected 21 MS patients &#40;2010 McDonald criteria&#41; with VS and VC impairment&#44; and 13 without CI &#40;control group&#41; out of a total of 100 MS patients&#46; All of these patients underwent routine and comprehensive neuropsychological assessment including IPS&#44; memory&#44; learning&#44; attention&#44; executive functions&#44; language processing&#44; and VS and VC skills&#46; We excluded patients with psychiatric disorders&#44; those under treatment with psychotropic drugs&#44; and patients with any visual impairment and&#47;or alteration of eye movements mentioned in their medical records&#44; due to the potential for interference with performance on cognitive tests&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">We recorded age&#44; sex&#44; type of MS&#44; degree of disability measured by the Expanded Disability Status Scale &#40;EDSS&#41;&#44; and MS progression time when the neuropsychological evaluation took place&#46; Level of education reported as years of schooling was also included&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Levels of depression &#40;Beck Depression Inventory&#41; and anxiety &#40;State-Trait Anxiety Inventory&#41; were analysed to control for their effect on cognitive performance&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Measurement instruments</span><p id="par0040" class="elsevierStylePara elsevierViewall">VS and VC skills were evaluated using the block design test &#40;BDT&#41; and the picture completion test &#40;PCT&#41; of the Wechsler Adult Intelligence Scale &#40;WAIS-III&#41;&#44; and the Rey&#8211;Osterrieth Complex Figure Test &#40;ROCF&#41;&#58; copy accuracy and immediate reproduction&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">BDT</span><p id="par0045" class="elsevierStylePara elsevierViewall">The patient recreates geometric designs using blocks&#46; This assesses the capacity to analyse and synthesise abstract geometrical drawings&#44; problem solution strategies&#44; psychomotor integration&#44; speed&#44; and distraction&#46; Scaled scores of &#8804;7 &#40;&#8804;&#8722;1 SD&#41; are considered abnormal&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">PCT</span><p id="par0050" class="elsevierStylePara elsevierViewall">Patients are provided with pictures of everyday objects with a part missing that they attempt to identify&#46; This is a time-dependent test that assesses the capacity to visually organise objects&#46; Scaled scores of &#8804;7 &#40;&#8804;&#8722;1 SD&#41; are considered abnormal&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Rey&#8211;Osterrieth complex figure</span><p id="par0055" class="elsevierStylePara elsevierViewall">This test analyses perceptual organisation and visual memory by asking the patient to reproduce a figure after an interference period&#46; It assesses the capacity to organise and plan strategies to resolve problems&#44; as well as VC skills&#46; Percentiles &#8804;30 indicate pathology due to the ceiling effect of this test &#40;most of the subjects obtain high scores at the upper part of the distribution&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Obtaining abnormal results in at least one test signified a VS and&#47;or VC skills deficit&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Measuring LV using magnetic resonance</span><p id="par0065" class="elsevierStylePara elsevierViewall">A brain MRI was conducted &#40;Siemens&#44; 1&#46;5<span class="elsevierStyleHsp" style=""></span>Tesla&#41;&#46; The MRI consisted of 5<span class="elsevierStyleHsp" style=""></span>mm slices of axial T1-weighted sequences and coronal Fluid-Attenuated Inversion Recovery &#40;FLAIR&#41; sequences&#44; which were used to identify and measure WM lesions&#46; WM LV was quantified in the parietal-temporal-occipital association area located between the postcentral and occipital sulci&#46; A researcher blinded to the results of the neuropsychological tests drew the lesion borders&#46; The area of each lesion was automatically calculated by the software that processes the MRI scans &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; WM LV of the region is calculated by adding the area of all lesions in all slices and multiplying the result by the slice thickness&#46; Linear measurements of brain atrophy are also conducted using the third ventricle width &#40;TVW&#41; and bicaudate ratio &#40;BCR&#41;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">23&#8211;25</span></a> derived from FLAIR sequences&#46; Time elapsed between the neuropsychological examination and the MRI was no longer than 3 months in any case&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">We used SPSS software version 18&#46;0&#46; We performed descriptive and frequency analyses for both groups&#46; We used the chi-square test &#40;categorical variables&#41; for calculating the inter-group comparison &#40;study group and control group&#41;&#44; and the <span class="elsevierStyleItalic">t</span>-test &#40;continuous variables&#41; for independent samples&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We analysed the relationship between VS&#8211;VC tasks and clinical and radiological variables in each MS patient&#44; with or without CI&#46; To do this&#44; we used bivariate and partial correlations&#44; and controlled for age and years of schooling &#40;Spearman rank&#41;&#46; We also used a linear regression model &#40;stepwise method&#41; employing each of the 3 cognitive tests as dependent variables&#44; while demographic and clinical variables and MRI measurements &#40;LV on T1-weighted images of the right&#44; left&#44; and both hemispheres&#44; and FLAIR LV images of the right&#44; left&#44; and both hemispheres&#44; TVW&#44; and BCR&#41; which showed a statistically significant relationship in the bivariate analysis were used as independent variables&#46; Age&#44; sex&#44; and years of schooling were always included in the model&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results</span><p id="par0080" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> includes the clinical and radiological characteristics of the 2 groups of MS patients&#46; We observed statistically significant differences between the control group &#40;MS patients without CI&#41; and the group of MS patients with impaired VS and VC skills regarding years of schooling&#44; EDSS score&#44; type of MS&#44; and all LV and subcortical atrophy MRI measurements &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Correlations</span><p id="par0085" class="elsevierStylePara elsevierViewall">We obtained no significant correlations between cognitive tests and sex&#44; type of MS&#44; or time of progression of MS&#46; Degree of depression &#40;Beck Depression Inventory&#58; PCT&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;081&#59; BDT&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;106&#59; ROCF <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;933&#41;&#44; and anxiety &#40;State-Trait Anxiety Inventory&#58; PCT&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;142&#59; BDT&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;134&#59; ROCF&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;126&#41; were not correlated with performance on the tests&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Education level significantly influenced the score on the 3 tests &#40;PCT&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;010&#59; BDT&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;005&#59; ROCF&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;014&#41; though age only influenced results on the ROCF test &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;005&#41;&#46; Therefore&#44; their effect is controlled in the bivariate correlations &#40;EDSS score and MRI measurements&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the variables which are significantly related to performance regarding VS&#8211;VC tasks&#46; Of special note is the strong inverse correlation with all LV and atrophy MRI measurements &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;01&#41; which remains after controlling for age and years of schooling&#44; except in the case of the PCT and central atrophy measurements&#46; FLAIR derived LV of the left and both hemispheres shows a stronger and more uniform correlation with the 3 tests than other volume measurements&#46; However&#44; the most marked association is seen between TVW and VC skills &#40;BDT and ROCF-copy accuracy&#44; r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;548&#47;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001 and r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;608&#47;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;000&#44; respectively&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Linear regression</span><p id="par0100" class="elsevierStylePara elsevierViewall">No clinical variable is able to explain performance on cognitive tests&#44; but years of schooling and age can explain VC performance &#40;ROCF&#41;&#46; Additionally&#44; TVW has an independent and statistically significant influence on VC performance &#40;BDT and ROCF&#41;&#46; We further observed an independent statistically significant effect of the regional FLAIR LV on VS tasks &#40;PCT&#41;&#44; with a lower impact &#40;considerable LV increases were required to notably modify test scores&#41;&#46; The remaining radiological variables do not show any statistically significant relationship &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">Impaired VS and VC skills were detected in 20&#37;-26&#37;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">3&#44;7&#44;20</span></a> of the MS patients&#46; This low percentage is surprising due to the observation&#44; on most of the patients&#8217; MRI scans&#44; of extensive WM involvement in the parieto-occipital and temporal-occipital areas&#44; the precise regions involved in these functions&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">21&#44;22</span></a> Several explanations can be put forward&#58; the tests used to routinely study CI in MS might have low sensitivity to impairment of these functions&#44; or alternatively&#44; these functions might require activation of low brain volume&#44; or are replaced by the extensive connections in these areas&#46; In this article&#44; we studied these functions with tests which are not routinely used for CI evaluation in MS&#46; However&#44; these tests are specific and largely standardised and validated for the analysis of these functions in a number of countries&#46; BDT and PCT &#40;WAIS III subtests&#41;&#44; and ROCF are well known tools that analyse complex visual perception and organisation tasks&#44; in addition to visuomotor and VC tasks&#46; Although this is a retrospective study with its associated weak points &#40;which we will analyse later&#41;&#44; its interest resides in the specific analysis of these functions and their relationship with structural changes in the brain areas involved in these tasks&#46; This approach has been only sporadically addressed in the literature &#40;as searched on MedLine&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">23&#44;26&#44;27</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In our study&#44; we have observed VS and VC task impairment in 21&#37; of the patients&#46; We are likely underestimating the true prevalence of impairment&#44; since we have excluded patients with any mention of even minimal symptoms or signs of visual impairment or ocular motility in their medical records in order to avoid bias when interpreting the results&#46; Vleugels et al&#46; found VS impairment in 26&#37; of the 49 patients studied with an extensive battery of tests specific to these skills&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">20</span></a> This is the highest frequency so far reported&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Our VS impaired MS patients have significantly higher EDSS scores&#44; more WM LV in the parietal-temporal-occipital association area&#44; and greater subcortical atrophy than MS patients with no CI at all&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">Many other authors have described the association between CI and EDSS scores&#44;<a class="elsevierStyleCrossRefs" href="#bib0225"><span class="elsevierStyleSup">7&#44;8&#44;11&#44;24</span></a> although it is a well-known fact that patients with little motor dysfunction can show substantial CI<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">12&#44;20</span></a> and that some domains such as IPS may be altered before motor function&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">6</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">We observed a significant inverse association between performance on the 3 tests &#40;PCT&#44; BDT&#44; and ROCF&#41; and all MRI measurements&#46; Regional FLAIR LV images showed a stronger correlation with all tests than T1-weighted sequence LV measurements&#44; while at the same time maintaining independent significance on multivariate analysis with regards to VS tasks&#44; although to a lesser extent&#46; T1-weighted LV images are better at revealing axonal damage&#44; which is not surprising since FLAIR sequences enable better identification of lesions and are more sensitive to periventricular and grey matter-WM interface lesions&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">28&#44;29</span></a> Correlations between T1 and T2-weighted LV images and CI have been only moderately and inconsistently mentioned in the medical literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">27&#44;30&#44;31</span></a> In contrast to our study&#44; Lazeron et al&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">24</span></a> did not find a correlation between VS processing and regional LV in a sample of 32 patients studied with an extensive battery which included only one VS processing test&#46; These results might be explained&#44; at least in part&#44; by differences among patients &#40;their patients were older and had higher EDSS scores&#41; and the test used &#40;they used a VS task with a significant VS memory load and did not assess VS skills&#41;&#46; This moderate and inconsistent correlation between LV and CI is partially explained by problems inherent to the measurement itself&#58; areas of inflammation&#44; oedema&#44; and gliosis are included in the assessment of volume&#44; which masks some WM atrophy&#59; cortical plaques are difficult to detect by conventional MRI and so are usually not included in the analysis&#44;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">32</span></a> and structural changes in normal-appearing WM&#44; with subsequent alteration in connectivity to cortical areas&#44; as has been demonstrated by anisotropy studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">31&#44;33</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Although both methods of brain atrophy evaluation &#40;BCR and TVW&#41; show a strong correlation with VS and VC impairment in 2 out of the 3 tests &#40;BDT&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;004 and &#46;001&#59; ROCF&#44; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;004 and &#46;000&#41;&#44; only TVW explains the variations in VC task results&#44; with a higher impact which is independent of education level&#46; By using the same indirect measurements&#44; other authors have observed a close association between subcortical atrophy and cognitive dysfunction&#46;<a class="elsevierStyleCrossRefs" href="#bib0305"><span class="elsevierStyleSup">23&#44;28&#44;34&#44;35</span></a> However&#44; only Benedict et al&#46; assess VS memory using the Brief Visuospatial Memory Test-Revised&#59; VC skills were not assessed&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">23</span></a> Increased BCR is related to extensive frontal WM atrophy while elevated TVW is associated with the volume of the thalamus&#44; a structure with extensive cortical connections&#46; To perform complex activities which involve organisation and praxis functions linked to frontal brain areas&#44; such as VC tasks&#44; this connectivity is hypothetically necessary&#46; The thalamus appears to be one of the brain regions with a higher prevalence of atrophy during the initial stages of MS&#46; It is also strongly correlated with physical and cognitive disability<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">36&#44;37</span></a> and is a good marker of poor outcome&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">38</span></a> Finally&#44; although both measurements &#40;BCR and TVW&#41; show an appreciable intra- and interobserver variability which depends on slice thickness&#44; they have demonstrated their usefulness in monitoring brain atrophy progression in comparison with SIENAX&#44; an automatic method for estimating brain volume which is widely used for cases of MS&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">25</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Our study does have some limitations&#46; For one thing&#44; it is a retrospective study with a small patient sample&#46; To minimise unavoidable variability in the acquisition of MR images&#44; a single researcher blinded to clinical and neuropsychological parameters performed all the LV and atrophy measurements&#46; Also&#44; the study area was previously established using fixed coordinates&#46; The same neuropsychologist evaluated all the patients in order to avoid biases in test administration&#46; Another study weakness is the effect of varying education levels in groups of MS patients with or without CI&#44; which is minimised in the data analysis adjusted for this parameter&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study analyses specific cognitive domains&#44; VC and VS tasks&#44; and their relationship with WM LV in parietal-temporal-occipital association areas&#44; and subcortical brain atrophy&#46; FLAIR LV and subcortical atrophy show a strong correlation with cognitive performance in these domains&#46; Subcortical atrophy&#44; estimated from TVW which measures thalamic atrophy&#44; is highly correlated with VC task impairment&#44; while regional LV is highly correlated with VS task impairment&#46; These results point to the need to extend the study and use automated LV measurements in a larger sample&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0145" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Marta Cerezo Gracia has been awarded a grant by <span class="elsevierStyleGrantSponsor" id="gs1">Merck Serono and BioGen</span> for the application of neuropsychological tests&#46;</p></span></span>"
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    "fechaRecibido" => "2015-02-22"
    "fechaAceptado" => "2015-06-04"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec640288"
          "palabras" => array:5 [
            0 => "Multiple sclerosis"
            1 => "Lesion volume"
            2 => "Cognitive impairment"
            3 => "Subcortical atrophy"
            4 => "Visuospatial&#47;visuoconstructional skills"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec640289"
          "palabras" => array:5 [
            0 => "Esclerosis m&#250;ltiple"
            1 => "Volumen lesional"
            2 => "D&#233;ficits cognitivos"
            3 => "Atrofia sucortical"
            4 => "Habilidades visuoespaciales&#47;visuoconstructivas"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">About 20&#37; to 26&#37; of patients with multiple sclerosis &#40;MS&#41; show alterations in visuospatial&#47;visuoconstructive &#40;VS&#8211;VC&#41; skills even though temporo-parieto-occipital impairment is a frequent finding in magnetic resonance imaging&#46; No studies have specifically analysed the relationship between these functions and lesion volume &#40;LV&#41; in these specific brain areas&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objective</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">To evaluate the relationship between VS&#8211;VC impairment and magnetic resonance imaging temporo-parieto-occipital LV with subcortical atrophy in patients with MS&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methodology</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Of 100 MS patients undergoing a routine neuropsychological evaluation&#44; 21 were selected because they displayed VS&#8211;VC impairments in the following tests&#58; incomplete picture&#44; block design &#40;WAIS-III&#41;&#44; and Rey&#8211;Osterrieth Complex Figure Test&#46; We also selected 13 MS patients without cognitive impairment &#40;control group&#41;&#46; Regional LV was measured in FLAIR and T1-weighted images using a semiautomated method&#59; subcortical atrophy was measured by bicaudate ratio and third ventricle width&#46; Partial correlations &#40;controlling for age and years of schooling&#41; and linear regression analysis were employed to analyse correlations between magnetic resonance imaging parameters and cognitive performance&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">All measures of LV and brain atrophy were significantly higher in patients with cognitive impairment&#46; Regional LV&#44; bicaudate ratio&#44; and third ventricle width are significantly and inversely correlated with cognitive performance&#59; the strongest correlation was between third ventricle width and VC performance &#40;block design&#58; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;001&#59; Rey&#8211;Osterrieth complex figure&#58; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;000&#41;&#46; In the multivariate analysis&#44; third ventricle width only had a significant effect on performance of VC tasks &#40;block design&#58; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;000&#59; Rey&#8211;Osterrieth complex figure&#58; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;000&#41;&#44; and regional FLAIR VL was linked to the VS task &#40;incomplete picture&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;002&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Measures of subcortical atrophy explain the variations in performance on visuocostructive tasks&#44; and regional FLAIR VL measures are linked to VS tasks&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objective"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methodology"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
          ]
          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Solo el 20-26&#37; de los pacientes con esclerosis m&#250;ltiple presenta d&#233;ficits en habilidades visuoespaciales-visuoconstructivas &#40;VE-VC&#41; pese a la frecuente afectaci&#243;n t&#233;mporo-parieto-occipital en resonancia magn&#233;tica&#46; No hay estudios que analicen la relaci&#243;n entre estas funciones y el volumen lesional &#40;VL&#41; de estas &#225;reas cerebrales&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluar la relaci&#243;n del VL parieto-occipito-temporal y la atrofia subcortical con el rendimiento en funciones VE-VC en esclerosis m&#250;ltiple&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Metodolog&#237;a</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">De 100 pacientes de esclerosis m&#250;ltiple con evaluaci&#243;n neuropsicol&#243;gica rutinaria se seleccionan 21 por afectaci&#243;n en habilidades VE-VC&#44; medidas por Figuras incompletas&#44; Cubos &#40;WAIS-III&#41; y Figura compleja de Rey-Osterrieth&#44; y 13 sin d&#233;ficit cognitivo &#40;grupo control&#41;&#46; El VL regional se cuantifica por un m&#233;todo semiautom&#225;tico en secuencias FLAIR y T1&#44; y la atrofia subcortical por el ratio bicaudado y la anchura del <span class="elsevierStyleSmallCaps">iii</span> ventr&#237;culo &#40;AIIIV&#41;&#46; Se utilizan correlaciones parciales &#40;controlando con edad y escolarizaci&#243;n&#41; y regresi&#243;n lineal para analizar la relaci&#243;n entre los par&#225;metros de resonancia magn&#233;tica y el rendimiento cognitivo&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Todas las medidas de VL y de atrofia cerebral son significativamente mayores en pacientes con deterioro cognitivo&#46; El VL regional en FLAIR&#44; ratio bicaudado y AIIIV muestran significativa correlaci&#243;n inversa con el rendimiento cognitivo&#44; mayor entre la AIIIV y VC &#40;Cubos&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#59; Figura compleja de Rey-Osterrieth&#58; p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;000&#41;&#46; En el an&#225;lisis multivariante&#44; la AIIIV influye significativamente en tareas de VC &#40;Cubos&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;000&#59; Figura compleja de Rey-Osterrieth&#58; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;000&#41; y el VL regional en FLAIR en tareas VE &#40;Figuras incompletas&#59; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;002&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Las medidas de atrofia subcortical se relacionan con tareas de visuoconstrucci&#243;n y el VL regional con tareas VE&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Introducci&#243;n"
          ]
          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivo"
          ]
          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Metodolog&#237;a"
          ]
          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
          ]
          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Please cite this article as&#58; Marasescu R&#44; Cerezo Garcia M&#44; Aladro Benito Y&#46; Afectaci&#243;n visuoespacial&#47;visuoconstrucci&#243;n en pacientes con esclerosis m&#250;ltiple&#46; Relaci&#243;n con el volumen lesional regional y la atrofia subcortical&#46; Neurolog&#237;a&#46; 2016&#59;31&#58;169&#8211;175&#46;</p>"
      ]
    ]
    "multimedia" => array:4 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Figure 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1057
            "Ancho" => 1800
            "Tamanyo" => 139779
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        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Lesions are manually marked and their area is automatically calculated by software specific for irregular areas&#46; Total LV is calculated by adding the area of all lesions and multiplying the result by slice thickness&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:3 [
          "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">TVW&#58; third ventricle width&#59; SD&#58; standard deviation&#59; EDSS&#58; Kurtzke Expanded Disability Status Scale&#59; FLAIR&#58; Fluid-Attenuated Inversion Recovery&#59; BVR&#58; bivariate ratio&#59; RR&#58; relapsing-remitting&#59; FLAIR LV&#58; lesion volume on a FLAIR MRI sequence&#59; T1 LV&#58; lesion volume on a T1-weighted MRI sequence&#46;</p>"
          "tablatextoimagen" => array:1 [
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study group<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Control group<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">40&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>12&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;31&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;229&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex&#58; women&#47;men &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#47;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;891&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EDSS scores &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;09<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;19<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;002<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">RR&#47;progressive &#40;<span class="elsevierStyleItalic">n</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#47;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#47;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;034<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Years of schooling &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;029<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Progression time in months &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">88&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>61&#46;69&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">77&#46;69<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>52&#46;84&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;582&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BVR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;15<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;046&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;017&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;005<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">TVW &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;75&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;88<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;000<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">FLAIR LV &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#44;694&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8575&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2548&#46;61<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3280&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;001<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">T1 LV &#40;mm<span class="elsevierStyleSup">3</span>&#41; &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6008&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6959&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">295&#46;42<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>647&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;006<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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            0 => array:3 [
              "identificador" => "tblfn0005"
              "etiqueta" => "&#42;"
              "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Significance level<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p>"
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        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Clinical and radiological characteristics&#46;</p>"
        ]
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        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">EDSS&#58; degree of disability according to the Expanded Disability Status Scale&#59; FLAIR&#58; Fluid-Attenuated Inversion Recovery&#59; MRI&#58; magnetic resonance imaging&#59; T1 LV&#58; lesion volume on a T1-weighted MRI sequence&#46;</p><p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">Significance level<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&#58; Age&#44; clinical variables&#44; MRI<br>Anxiety&#44; depression&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Picture completion &#40;<span class="elsevierStyleItalic">r</span>&#47;<span class="elsevierStyleItalic">P</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Block design &#40;<span class="elsevierStyleItalic">r</span>&#47;<span class="elsevierStyleItalic">P</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rey&#8211;Osterrieth complex figure &#40;i&#47;<span class="elsevierStyleItalic">P</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EDSS score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;506&#47;&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;580&#47;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;560&#47;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on right axial T1-weighted image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;520&#47;&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;444&#47;&#46;012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;389&#47;&#46;031&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on left axial T1-weighted image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;515&#47;&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;445&#47;&#46;012&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;437&#47;&#46;014&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total LV on axial T1-weighted image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;523&#47;&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;449&#47;&#46;011&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;417&#47;&#46;019&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on right coronal FLAIR image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;515&#47;&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;517&#47;&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;456&#47;&#46;010&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on left coronal FLAIR image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;505&#47;&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;504&#47;&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;507&#47;&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total LV on coronal FLAIR image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;524&#47;&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;513&#47;&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;514&#47;&#46;003&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bicaudate ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;323&#47;&#46;077&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;500&#47;&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;503&#47;&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Third ventricle width &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;276&#47;&#46;133&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;548&#47;&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;608&#47;&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Partial correlations between EDSS scores&#44; LV on T1-weighted sequences&#44; FLAIR&#59; atrophy measurements and cognitive tests&#44; adjusted for age and level of education&#46;</p>"
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          "leyenda" => "<p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">EDSS&#58; degree of disability according to the Expanded Disability Status Scale&#59; FLAIR&#58; Fluid-Attenuated Inversion Recovery&#59; MRI&#58; magnetic resonance imaging&#59; VC&#58; visuoconstructive&#59; VS&#58; visuospatial&#59; T1 LV&#58; lesion volume on a T1-weighted MRI sequence&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MRI measurements&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Figure completion &#40;<span class="elsevierStyleItalic">P</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Block design &#40;<span class="elsevierStyleItalic">P</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Rey&#8211;Osterrieth complex figure &#40;<span class="elsevierStyleItalic">P</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on right axial T1-weighted image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;518&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;210&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;860&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on left axial T1-weighted image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;326&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;227&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;965&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total LV on axial T1-weighted image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;390&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;214&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;911&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on right coronal FLAIR image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;576&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;217&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;664&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">LV on left coronal FLAIR image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;315&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;217&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;513&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total LV on coronal FLAIR image &#40;mm<span class="elsevierStyleSup">3</span>&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;002<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;190&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;906&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bicaudate ratio&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;575&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;688&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;921&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Third ventricle width &#40;mm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;968&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;000<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;000<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;721&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;004<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;618&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;115&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;448&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Education &#40;in years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;008<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;014<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;042<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">&#42;</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">EDSS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;333&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;&#46;207&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;199&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Progression timeline&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;488&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;333&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#46;689&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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              "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Significance level<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>&#46;05&#46;</p>"
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Linear regression to evaluate the effect of MRI parameters on VS&#8211;VC tasks&#46;</p>"
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    "bibliografia" => array:2 [
      "titulo" => "References"
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        0 => array:2 [
          "identificador" => "bibs0005"
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            0 => array:3 [
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                      "titulo" => "Risk factors for and management of cognitive dysfunction in multiple sclerosis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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Article information

ISSN: 21735808
Original language: English

DOI:10.1016/j.nrleng.2015.06.006

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Year/Month	Html	Pdf	Total

2024 November	4	0	4
2024 October	21	1	22
2024 September	27	3	30
2024 August	33	3	36
2024 July	20	3	23
2024 June	22	1	23
2024 May	16	3	19
2024 April	22	3	25
2024 March	27	3	30
2024 February	19	6	25
2024 January	16	4	20
2023 December	10	4	14
2023 November	15	7	22
2023 October	24	8	32
2023 September	13	2	15
2023 August	20	6	26
2023 July	8	5	13
2023 June	22	3	25
2023 May	42	6	48
2023 April	41	2	43
2023 March	23	0	23
2023 February	29	2	31
2023 January	11	6	17
2022 December	28	3	31
2022 November	25	6	31
2022 October	17	21	38
2022 September	19	30	49
2022 August	27	12	39
2022 July	14	6	20
2022 June	16	4	20
2022 May	31	7	38
2022 April	67	18	85
2022 March	49	10	59
2022 February	34	4	38
2022 January	78	3	81
2021 December	55	11	66
2021 November	20	8	28
2021 October	53	8	61
2021 September	37	9	46
2021 August	39	12	51
2021 July	28	5	33
2021 June	28	8	36
2021 May	34	21	55
2021 April	127	17	144
2021 March	51	9	60
2021 February	31	9	40
2021 January	41	17	58
2020 December	23	13	36
2020 November	32	13	45
2020 October	20	8	28
2020 September	27	11	38
2020 August	26	7	33
2020 July	17	11	28
2020 June	11	12	23
2020 May	16	18	34
2020 April	10	2	12
2020 March	16	2	18
2020 February	13	13	26
2020 January	20	11	31
2019 December	20	7	27
2019 November	14	7	21
2019 October	8	3	11
2019 September	11	10	21
2019 August	19	11	30
2019 July	7	13	20
2019 June	18	26	44
2019 May	73	41	114
2019 April	19	9	28
2019 March	8	12	20
2019 February	10	16	26
2019 January	9	10	19
2018 December	9	1	10
2018 November	10	4	14
2018 October	16	4	20
2018 September	16	10	26
2018 August	11	6	17
2018 July	8	1	9
2018 June	7	8	15
2018 May	14	4	18
2018 April	6	6	12
2018 March	3	2	5
2018 February	3	4	7
2018 January	8	9	17
2017 December	4	0	4
2017 November	8	4	12
2017 October	5	3	8
2017 September	7	3	10
2017 August	11	6	17
2017 July	11	0	11
2017 June	10	7	17
2017 May	6	3	9
2017 April	9	3	12
2017 March	8	29	37
2017 February	15	3	18
2017 January	14	2	16
2016 December	8	3	11
2016 November	15	5	20
2016 October	21	6	27
2016 September	38	2	40
2016 August	33	6	39
2016 July	25	6	31
2016 June	32	9	41
2016 May	32	18	50
2016 April	35	13	48

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