Papers by Pablo Villoslada
PLOS ONE, 2015
In order to retrieve useful information from scientific literature and electronic medical records... more In order to retrieve useful information from scientific literature and electronic medical records (EMR) we developed an ontology specific for Multiple Sclerosis (MS).
Clinical validation of MsdiagTM test for predicting Multiple Sclerosis activity
ABSTRACT
Language is frequently impaired in multiple sclerosis (MS) in which, in addition to dysarthria an... more Language is frequently impaired in multiple sclerosis (MS) in which, in addition to dysarthria and loss of fluency, other language deficits might affect patients and impinge on their quality of life.
CPT: Pharmacometrics & Systems Pharmacology, 2015
In patients with relapsing-remitting multiple sclerosis (RRMS), interferon beta-1b (IFNb-1b) redu... more In patients with relapsing-remitting multiple sclerosis (RRMS), interferon beta-1b (IFNb-1b) reduces the occurrence of contrast enhancing lesions (CELs) on magnetic resonance imaging (MRI). Questions remain on the stability of IFNb-1b effect over time and its action beyond the reduction of CELs. In this study, we described the IFNb-1b effect by a mixed effects model, quantifying the interpatient variability associated with its parameters. Using a negative binomial distribution model as a natural history model, the effect of IFNb-1b was evaluated using different mathematical functions of time. IFNb-1b produced a decrease in the expected CEL numbers, inhibiting the formation of new CELs but did not promote the resolution of the already-formed ones. Based on the final selected model, simulations were carried out to optimize the combined IFNb-1bcorticosteroid therapy as a proof-of-concept. In summary, we provide evidence on the dynamics of CELs under IFNb-1b treatment that can be used to monitor the effects of therapies in MS.
Pituitary-ovary axis and ovarian reserve in fertile women with multiple sclerosis: A pilot study
Multiple sclerosis (Houndmills, Basingstoke, England), Jan 11, 2015
Since a decline in the ovary function might impact the reproductive potential in women with multi... more Since a decline in the ovary function might impact the reproductive potential in women with multiple sclerosis (MS), we investigated the pituitary-ovary axis and ovarian reserve, including anti-Müllerian hormone (AMH) levels and ultrasound imaging of the ovaries, of 25 relapsing-remitting MS patients and 25 age-matched healthy controls. Mean levels of pituitary-gonadal hormones and age-adjusted parameters of ovarian reserve markers were not significantly different between both groups. Patients with higher disease activity (annualized relapse rate >0.5; n=9) had significantly lower AMH levels, total antral follicle count and ovarian volume, than those with lower disease activity. The finding of poorer ovarian reserve associated with higher disease activity should be taken into consideration since it may negatively impact the reproductive prognosis.
Improved Framework for Tractography Reconstruction of the Optic Radiation
PloS one, 2015
The optic radiation (OR) is one of the major components of the visual system and a key structure ... more The optic radiation (OR) is one of the major components of the visual system and a key structure at risk in white matter diseases such as multiple sclerosis (MS). However, it is challenging to perform track reconstruction of the OR using diffusion MRI due to a sharp change of direction in the Meyer's loop and the presence of kissing and crossing fibers along the pathway. As such, we aimed to provide a highly precise and reproducible framework for tracking the OR from thalamic and visual cortex masks. The framework combined the generation of probabilistic streamlines by high order fiber orientation distributions estimated with constrained spherical deconvolution and an automatic post-processing based on anatomical exclusion criteria (AEC) to compensate for the presence of anatomically implausible streamlines. Specifically, those ending in the contralateral hemisphere, cerebrospinal fluid or grey matter outside the visual cortex were automatically excluded. We applied the framewor...
[Usefulness of serial cranial MR in isolated myelitis for the diagnosis of multiple sclerosis]
Medicina Clínica
Acute optic neuritis: Unmet clinical needs and model for new therapies
Neurology® neuroimmunology & neuroinflammation, 2015
Idiopathic demyelinating optic neuritis (ON) most commonly presents as acute unilateral vision lo... more Idiopathic demyelinating optic neuritis (ON) most commonly presents as acute unilateral vision loss and eye pain and is frequently associated with multiple sclerosis. Although emphasis is often placed on the good recovery of high-contrast visual acuity, persistent deficits are frequently observed in other aspects of vision, including contrast sensitivity, visual field testing, color vision, motion perception, and vision-related quality of life. Persistent and profound structural and functional changes are often revealed by imaging and electrophysiologic techniques, including optical coherence tomography, visual-evoked potentials, and nonconventional MRI. These abnormalities can impair patients' abilities to perform daily activities (e.g., driving, working) so they have important implications for patients' quality of life. In this article, we review the sequelae from ON, including clinical, structural, and functional changes and their interrelationships. The unmet needs in ea...
Mathematics and Visualization, 2015
Diffusion weighted magnetic resonance imaging (dMRI) and tractogra-5 phy have shown great potenti... more Diffusion weighted magnetic resonance imaging (dMRI) and tractogra-5 phy have shown great potential for the investigation of the white mater architecture 6 in-vivo, especially with the recent advancements by using higher order techniques 7 to model the data. Many clinical applications ranging from neurodegenerative 8 disorders, psychiatric disorders as well as pre-surgical planning employ diffusion 9 imaging-based analysis as an addition to conventional MRI imaging. However, 10 despite the promising outlook, dMRI tractography confronts many challenges that 11 complicate its use in everyday clinical practice. Some of these challenges are 12 low test-retest accuracy, poor quantification of tracts size, poor understanding of 13 the biological basis of the dMRI parameters, inaccuracies in the geometry of the 14 reconstructed streamlines (especially in complex areas with curvature, bifurcations, 15 fanning, crossings), poor alignment with the neighboring diffusion profiles, among 16 others. Recently developed contextual processing techniques including the one 17 presented in this work, for enhancement and well-posed geometric sharpening, have 18
Goals and pitfalls of gene network inference methods: a comparative study from virtual microarrays and network dynamics
Introduction: Retinal periphlebitis (RP) is characterized by perivascular exudation, hemorrhage, ... more Introduction: Retinal periphlebitis (RP) is characterized by perivascular exudation, hemorrhage, and retinal venous sheathing. The relationship between RP and multiple sclerosis (MS) is known and has a variable incidence among series (5-39%). RP has been related to a more active disease (1). Retinal inflammation parallels the inflamatory processes in the central nervous system and his presence of RP might favor the election of a more effective drug, even assuming a greater risk of side effects. The objetive of this study was evaluate the role of wide-field retinography to detect periphlebitis in patients without ocular symptoms. Methods: A prospective cohort including 118 patients with remittent-recurrent multiple sclerosis (aged 18–55 years), underwent a ophthalmic examination, between May/2013 to May/2014. We collected demographic and MS-related variables, measured high- and low-contrast monocular visual acuity using ETDRS (Early Treatment Diabetic Retinopathy Study), Color vision...
Introduction: Peripheral neuropathy secondary to drugs is a cause of severe disability. Usually I... more Introduction: Peripheral neuropathy secondary to drugs is a cause of severe disability. Usually Invasive techniques as cutaneous nerve biopsy are employed for diagnosis. Corneal confocal microscopy (CCM) is a noninvasive and rapid technique to assess in vivo all structures of the cornea, including the sub-basal nerve plexus. We designed a prospective study to evaluate the usefulness of CCM for determinate peripheral neuropathy. Methods: Ten patients with a high probability of developing peripheral neuropathy secondary to drug treatment were evaluated. Specifically, patients who started treatment with taxanes, cisplatin and / or oxaliplatin.No patients with prior use of chemotherapy, previous corneal surgery or infection and /or contact lenses were included in the study.The patients were visited before treatment and two, four months, at the end of chemotherapy and 3 months after treatment. These images were subsequently analyzed by CCmetrics Software (Manchester University) analyzing...
Structural connectivity matrices are a powerful tool largely used in many areas of neuroscience. ... more Structural connectivity matrices are a powerful tool largely used in many areas of neuroscience. In multiple sclerosis (MS) the presence of lesions in the white matter (WM) prevents proper streamline tracking, thus affecting metrics of the connectivity matrices. Our aim is to assess this effect with an enhanced representation of the connectivity that will provide researchers with better ways to understand and compare connectomes. MRI acquisitions were performed on 10 healthy volunteers and 5 MS patients using a 3T Siemens scanner. The MRI protocol included a 3D structural T1-MPRAGE and a HARDI. We have calculated the anatomical atlas for each subject and computed the whole brain tracking using deterministic tracking from tensors and from 6th and 8th order spherical harmonics. Instead of representing the connectome as an adjacency matrix of the normalized connectivity, we put all the edges in a single row and defined this as the connectivity spectrum. This representation shows the co...
Journal of Neuroinflammation
Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (... more Glutamate excitotoxicity contributes to oligodendrocyte and tissue damage in multiple sclerosis (MS). Intriguingly, glutamate level in plasma and cerebrospinal fluid of MS patients is elevated, a feature which may be related to the pathophysiology of this disease. In addition to glutamate transporters, levels of extracellular glutamate are controlled by cystine/glutamate antiporter x(c)⁻, an exchanger that provides intracellular cystine for production of glutathione, the major cellular antioxidant. The objective of this study was to analyze the role of the system x(c)⁻ in glutamate homeostasis alterations in MS pathology. Primary cultures of human monocytes and the cell line U-937 were used to investigate the mechanism of glutamate release. Expression of cystine glutamate exchanger (xCT) was quantified by quantitative PCR, Western blot, flow cytometry and immunohistochemistry in monocytes in vitro, in animals with experimental autoimmune encephalomyelitis (EAE), the animal model of ...
PLOS One, 2011
Negotiation and trade typically require a mutual interaction while simultaneously resting in unce... more Negotiation and trade typically require a mutual interaction while simultaneously resting in uncertainty which decision the partner ultimately will make at the end of the process. Assessing already during the negotiation in which direction one's counterpart tends would provide a tremendous advantage. Recently, neuroimaging techniques combined with multivariate pattern classification of the acquired data have made it possible to discriminate
Graefe's Archive for Clinical and Experimental Ophthalmology, 2015
Purpose To characterise the changes of the retinal layers in patients with acute anterior ischaem... more Purpose To characterise the changes of the retinal layers in patients with acute anterior ischaemic optic neuropathy (AION), aiming to identify imaging markers for predicting the residual visual function. Methods This was a retrospective review of consecutive patients with unilateral AION from January 2010 to December 2013. We analysed affected eyes at baseline and 1 month later, compared to fellow healthy eyes. Utilising novel image analysis software, we conducted algorithmic segmentation in layers and division in early treatment of diabetic retinopathy study (ETDRS) quadrants of optical coherence tomography images of the macula. Pearson product moment regression analysis of retinal layer thickness and best corrected visual acuity (BCVA) in logMAR units and mean deviation of the SITA 24-2 visual field (VF) were carried out at the 1-month time point. Results Twenty eyes from 20 patients were included and compared to 20 healthy fellow eyes. At baseline, we found a significantly increased mean thickness of the retinal nerve fibre layer (RNFL) of 42.2 μm (±6.7SD) in AION eyes compared to 37.9 μm (±4.2 SD) in healthy eyes (p=0.002). The outer nuclear layer (ONL) was also significantly thickened at 96.6 μm (±7.2 SD) compared to 90.8 μm (±5.7 SD) in the fellow eye (p<0.001). After 1 month, the RNFL and the ganglion cell layer (GCL) were thinned 17.7 % [to 31.2 μm (±6.4 SD), p<0.001] and 19.3 % [to 66.5 μm (±7.0 SD), p<0.001] compared to the contralateral eye. Additionally, the ONL remained thickened at 96.7 μm (±7.0 SD, p<0.001). At baseline, we found a significant correlation between the ONL thickness and the VF (r=−0.482, p=0.005) and the BCVA at discharge (r=0.552, p<0.001), indicating that a thicker ONL correlates with poorer visual function. The GCL thickness also correlates with the BCVA at discharge (r=0.411, p= 0.02), where a thinner GCL predicts worse BCVA. At the 1month time point, the GCL thinning was correlated with both the VF (r=0.471, p=0.005) and the BCVA (r=−0.456, p= 0.007), indicating worse visual function. Conclusions Changes in the thickness of different layers of the retina occur early in the course of AION and evolve over time, resulting in the atrophy of the GCL and RNFL. ONL thickening at baseline is associated with visual dysfunction. Thinning of the GCL after 1 month correlates with poorer VF and BCVA at 1 month after acute AION.
JAMA neurology, Jan 26, 2015
Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI... more Brain parenchymal lesions are frequently observed on conventional magnetic resonance imaging (MRI) scans of patients with neuromyelitis optica (NMO) spectrum disorder, but the specific morphological and temporal patterns distinguishing them unequivocally from lesions caused by other disorders have not been identified. This literature review summarizes the literature on advanced quantitative imaging measures reported for patients with NMO spectrum disorder, including proton MR spectroscopy, diffusion tensor imaging, magnetization transfer imaging, quantitative MR volumetry, and ultrahigh-field strength MRI. It was undertaken to consider the advanced MRI techniques used for patients with NMO by different specialists in the field. Although quantitative measures such as proton MR spectroscopy or magnetization transfer imaging have not reproducibly revealed diffuse brain injury, preliminary data from diffusion-weighted imaging and brain tissue volumetry indicate greater white matter than...
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Papers by Pablo Villoslada