30 results on '"Pulido-Valdeolivas, Irene"'
Search Results
2. Predicting disease severity in multiple sclerosis using multimodal data and machine learning.
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Andorra, Magi, Freire, Ana, Zubizarreta, Irati, de Rosbo, Nicole Kerlero, Bos, Steffan D., Rinas, Melanie, Høgestøl, Einar A., de Rodez Benavent, Sigrid A., Berge, Tone, Brune-Ingebretse, Synne, Ivaldi, Federico, Cellerino, Maria, Pardini, Matteo, Vila, Gemma, Pulido-Valdeolivas, Irene, Martinez-Lapiscina, Elena H., Llufriu, Sara, Saiz, Albert, Blanco, Yolanda, and Martinez-Heras, Eloy
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MACHINE learning ,MULTIPLE sclerosis ,RANDOM forest algorithms ,MONONUCLEAR leukocytes ,OPTICAL coherence tomography ,VENOUS insufficiency - Abstract
Background: Multiple sclerosis patients would benefit from machine learning algorithms that integrates clinical, imaging and multimodal biomarkers to define the risk of disease activity. Methods: We have analysed a prospective multi-centric cohort of 322 MS patients and 98 healthy controls from four MS centres, collecting disability scales at baseline and 2 years later. Imaging data included brain MRI and optical coherence tomography, and omics included genotyping, cytomics and phosphoproteomic data from peripheral blood mononuclear cells. Predictors of clinical outcomes were searched using Random Forest algorithms. Assessment of the algorithm performance was conducted in an independent prospective cohort of 271 MS patients from a single centre. Results: We found algorithms for predicting confirmed disability accumulation for the different scales, no evidence of disease activity (NEDA), onset of immunotherapy and the escalation from low- to high-efficacy therapy with intermediate to high-accuracy. This accuracy was achieved for most of the predictors using clinical data alone or in combination with imaging data. Still, in some cases, the addition of omics data slightly increased algorithm performance. Accuracies were comparable in both cohorts. Conclusion: Combining clinical, imaging and omics data with machine learning helps identify MS patients at risk of disability worsening. [ABSTRACT FROM AUTHOR]
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- 2024
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3. Toward an Automatic Assessment of Cognitive Dysfunction in Relapsing–Remitting Multiple Sclerosis Patients Using Eye Movement Analysis.
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García Cena, Cecilia E., Gómez-Andrés, David, Pulido-Valdeolivas, Irene, Sánchez-Seco, Victoria Galán, Domingo-Santos, Angela, Moreno-García, Sara, and Benito-León, Julián
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EYE movements ,GAZE ,COGNITION disorders ,MULTIPLE sclerosis ,DISEASE relapse ,EYE abnormalities ,DISEASE duration - Abstract
Despite the importance of cognitive function in multiple sclerosis, it is poorly represented in the Expanded Disability Status Scale (EDSS), the commonly used clinical measure to assess disability, suggesting that an analysis of eye movement, which is generated by an extensive and well-coordinated functional network that is engaged in cognitive function, could have the potential to extend and complement this more conventional measure. We aimed to measure the eye movement of a case series of MS patients with relapsing–remitting MS to assess their cognitive status using a conventional gaze tracker. A total of 41 relapsing–remitting MS patients and 43 age-matched healthy controls were recruited for this study. Overall, we could not find a clear common pattern in the eye motor abnormalities. Vertical eye movement was more impaired in MS patients than horizontal movement. Increased latencies were found in the prosaccades and reflexive saccades of antisaccade tests. The smooth pursuit was impaired with more corrections (backup and catchup movements, p < 0.01 ). No correlation was found between eye movement variables and EDSS or disease duration. Despite significant alterations in the behavior of the eye movements in MS patients, which are compatible with altered cognitive status, there is no common pattern of these alterations. We interpret this as a consequence of the patchy, heterogeneous distribution of white matter involvement in MS that provokes multiple combinations of impairment at different points in the different networks involved in eye motor control. Further studies are therefore required. [ABSTRACT FROM AUTHOR]
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- 2022
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4. Serum neurofilament light chain concentration predicts disease worsening in multiple sclerosis.
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Brune, Synne, Høgestøl, Einar A, de Rodez Benavent, Sigrid A, Berg-Hansen, Pål, Beyer, Mona K, Leikfoss, Ingvild Sørum, Bos, Steffan D, Sowa, Piotr, Brunborg, Cathrine, Andorra, Magi, Pulido Valdeolivas, Irene, Asseyer, Susanna, Brandt, Alexander, Chien, Claudia, Scheel, Michael, Blennow, Kaj, Zetterberg, Henrik, Kerlero de Rosbo, Nicole, Paul, Friedemann, and Uccelli, Antonio
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MULTIPLE sclerosis ,CYTOPLASMIC filaments ,OPTICAL coherence tomography ,MAGNETIC resonance imaging ,SINGLE molecules - Abstract
Background: Serum neurofilament light (sNfL) chain is a promising biomarker reflecting neuro-axonal injury in multiple sclerosis (MS). However, the ability of sNfL to predict outcomes in real-world MS cohorts requires further validation. Objective: The aim of the study is to investigate the associations of sNfL concentration, magnetic resonance imaging (MRI) and retinal optical coherence tomography (OCT) markers with disease worsening in a longitudinal European multicentre MS cohort. Methods: MS patients (n = 309) were prospectively enrolled at four centres and re-examined after 2 years (n = 226). NfL concentration was measured by single molecule array assay in serum. The patients' phenotypes were thoroughly characterized with clinical examination, retinal OCT and MRI brain scans. The primary outcome was disease worsening at median 2-year follow-up. Results: Patients with high sNfL concentrations (⩾8 pg/mL) at baseline had increased risk of disease worsening at median 2-year follow-up (odds ratio (95% confidence interval) = 2.8 (1.5–5.3), p = 0.001). We found no significant associations of MRI or OCT measures at baseline with risk of disease worsening. Conclusion: Serum NfL concentration was the only factor associated with disease worsening, indicating that sNfL is a useful biomarker in MS that might be relevant in a clinical setting. [ABSTRACT FROM AUTHOR]
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- 2022
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5. Oligoclonal IgM bands in the cerebrospinal fluid of patients with relapsing MS to inform long-term MS disability.
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Capuano, Rocco, Zubizarreta, Irati, Alba-Arbalat, Salut, Sepulveda, María, Sola-Valls, Nuria, Pulido-Valdeolivas, Irene, Andorra, Magi, Martinez-Heras, Eloy, Solana, Elisabeth, Lopez-Soley, Elisabet, Montejo, Carmen, Blanco, Yolanda, Fernández-Velasco, Jose Ignacio, Gallo, Antonio, Bisecco, Alvino, Villoslada, Pablo, Saiz, Albert, Llufriu, Sara, Villar, Luisa M, and Martinez-Lapiscina, Elena H
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CEREBROSPINAL fluid ,DISABILITIES ,DISEASE relapse ,PROGNOSIS ,DRUG accessibility ,OPTIC neuritis ,NEUROMYELITIS optica - Abstract
Background: Prognostic markers are needed to guide multiple sclerosis (MS) management in the context of large availability of disease-modifying drugs (DMDs). Objective: To investigate the role of cerebrospinal fluid (CSF) markers to inform long-term MS outcomes. Methods: Demographic features, IgM index, oligoclonal IgM bands (OCMB), lipid-specific OCMB, CSF neurofilament light chain protein levels, expanded disability status scale (EDSS), relapses and DMD use over the study period and peripapillary retinal nerve fiber layer (pRNFL) and ganglion cell plus inner plexiform layer (GCIPL) thicknesses in non-optic neuritis eyes (end of follow-up) were collected from relapsing MS (RMS) patients with CSF obtained ⩽2 years after MS onset prospectively followed at the Hospital Clinic of Barcelona. We assessed associations between CSF markers and MS outcomes using multivariable models. Results: A total of 89 patients (71 females; median 32.9 years of age) followed over a median of 9.6 years were included. OCMB were associated with a 33% increase in the annualized relapse rate (ARR; p = 0.06), higher odds for high-efficacy DMDs use (OR = 4.8; 95% CI = (1.5, 16.1)), thinner pRNFL (β = −4.4; 95% CI = (−8.6, −0.2)) and GCIPL (β = −2.9; 95% CI = (−5.9, +0.05)), and higher rates to EDSS ⩾ 3.0 (HR = 4.4; 95% CI = (1.6, 11.8)) and EDSS ⩾ 4.0 (HR = 5.4; 95% CI = (1.1, 27.1)). No overall associations were found for other CSF markers. Conclusion: The presence of OCMB was associated with unfavorable long-term outcomes. OCMB should be determined in RMS to inform long-term prognosis. [ABSTRACT FROM AUTHOR]
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- 2021
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6. Regional grey matter microstructural changes and volume loss according to disease duration in multiple sclerosis patients.
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Solana, Elisabeth, Martinez-Heras, Eloy, Montal, Victor, Vilaplana, Eduard, Lopez-Soley, Elisabet, Radua, Joaquim, Sola-Valls, Nuria, Montejo, Carmen, Blanco, Yolanda, Pulido-Valdeolivas, Irene, Sepúlveda, Maria, Andorra, Magi, Berenguer, Joan, Villoslada, Pablo, Martinez-Lapiscina, E. H., Prados, Ferran, Saiz, Albert, Fortea, Juan, and Llufriu, Sara
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GRAY matter (Nerve tissue) ,MULTIPLE sclerosis ,DISEASE duration ,MAGNETIC resonance imaging of the brain ,CEREBRAL cortex - Abstract
The spatio-temporal characteristics of grey matter (GM) impairment in multiple sclerosis (MS) are poorly understood. We used a new surface-based diffusion MRI processing tool to investigate regional modifications of microstructure, and we quantified volume loss in GM in a cohort of patients with MS classified into three groups according to disease duration. Additionally, we investigated the relationship between GM changes with disease severity. We studied 54 healthy controls and 247 MS patients classified regarding disease duration: MS1 (less than 5 years, n = 67); MS2 (5–15 years, n = 107); and MS3 (more than15 years, n = 73). We compared GM mean diffusivity (MD), fractional anisotropy (FA) and volume between groups, and estimated their clinical associations. Regional modifications in diffusion measures (MD and FA) and volume did not overlap early in the disease, and became widespread in later phases. We found higher MD in MS1 group, mainly in the temporal cortex, and volume reduction in deep GM and left precuneus. Additional MD changes were evident in cingulate and occipital cortices in the MS2 group, coupled to volume reductions in deep GM and parietal and frontal poles. Changes in MD and volume extended to more than 80% of regions in MS3 group. Conversely, increments in FA, with very low effect size, were observed in the parietal cortex and thalamus in MS1 and MS2 groups, and extended to the frontal lobe in the later group. MD and GM changes were associated with white matter lesion load and with physical and cognitive disability. Microstructural integrity loss and atrophy present differential spatial predominance early in MS and accrual over time, probably due to distinct pathogenic mechanisms that underlie tissue damage. [ABSTRACT FROM AUTHOR]
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- 2021
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7. Disease duration and disability in dysfeRlinopathy can be described by muscle imaging using heatmaps and random forests.
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Gómez‐Andrés, David, Díaz, Jorge, Munell, Francina, Sánchez‐Montáñez, Ángel, Pulido‐Valdeolivas, Irene, Suazo, Lionel, Garrido, Cristián, Quijano‐Roy, Susana, Bevilacqua, Jorge A., Gómez-Andrés, David, Sánchez-Montáñez, Ángel, Pulido-Valdeolivas, Irene, and Quijano-Roy, Susana
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ADIPOSE tissues ,COMPARATIVE studies ,FUNCTIONAL assessment ,MAGNETIC resonance imaging ,RESEARCH methodology ,MEDICAL cooperation ,MUSCULAR dystrophy ,RESEARCH ,RESEARCH funding ,ROTATOR cuff ,EVALUATION research ,FIBROSIS ,PREDICTIVE tests ,SKELETAL muscle - Abstract
Introduction: The manner in which imaging patterns change over the disease course and with increasing disability in dysferlinopathy is not fully understood.Methods: Fibroadipose infiltration of 61 muscles was scored based on whole-body MRI of 33 patients with dysferlinopathy and represented in a heatmap. We trained random forests to predict disease duration, Motor Function Measure dimension 1 (MFM-D1), and modified Rankin scale (MRS) score based on muscle scoring and selected the most important muscle for predictions.Results: The heatmap delineated positive and negative fingerprints in dysferlinopathy. Disease duration was related to infiltration of infraspinatus, teres major-minor, and supraspinatus muscles. MFM-D1 decreased with higher infiltration of teres major-minor, triceps, and sartorius. MRS related to infiltration of vastus medialis, gracilis, infraspinatus, and sartorius.Discussion: Dysferlinopathy shows a recognizable muscle MRI pattern. Fibroadipose infiltration in specific muscles of the thigh and the upper limb appears to be an important marker for disease progression. Muscle Nerve 59:436-444, 2019. [ABSTRACT FROM AUTHOR]- Published
- 2019
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8. Incidence and Impact of COVID-19 in MS A Survey From a Barcelona MS Unit.
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Sepúlveda, Maria, Llufriu, Sara, Martínez-Herńandez, Eugenia, Catala, Martí, Artola, Montse, Hernando, Ana, Montejo, Carmen, Pulido-Valdeolivas, Irene, Martnez-Heras, Eloy, Guasp, Mar, Solana, Elisabeth, Llansó, Laura, Escudero, Domingo, Aldea, Marta, Prats, Clara, Graus, Francesc, Blanco, Yolanda, and Saiz, Albert
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- 2021
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9. Impact of Cognitive Reserve and Structural Connectivity on Cognitive Performance in Multiple Sclerosis.
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Lopez-Soley, Elisabet, Solana, Elisabeth, Martínez-Heras, Eloy, Andorra, Magi, Radua, Joaquim, Prats-Uribe, Albert, Montejo, Carmen, Sola-Valls, Nuria, Sepulveda, Maria, Pulido-Valdeolivas, Irene, Blanco, Yolanda, Martinez-Lapiscina, Elena H., Saiz, Albert, and Llufriu, Sara
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MULTIPLE sclerosis ,GRAY matter (Nerve tissue) ,MULTIPLE regression analysis ,COGNITION disorders ,BRAIN damage - Abstract
Background: Cognitive reserve (CR) could attenuate the impact of the brain burden on the cognition in people with multiple sclerosis (PwMS). Objective: To explore the relationship between CR and structural brain connectivity and investigate their role on cognition in PwMS cognitively impaired (PwMS-CI) and cognitively preserved (PwMS-CP). Methods: In this study, 181 PwMS (71% female; 42.9 ± 10.0 years) were evaluated using the Cognitive Reserve Questionnaire (CRQ), Brief Repeatable Battery of Neuropsychological tests, and MRI. Brain lesion and gray matter volumes were quantified, as was the structural network connectivity. Patients were classified as PwMS-CI (z scores = −1.5 SD in at least two tests) or PwMS-CP. Linear and multiple regression analyses were run to evaluate the association of CRQ and structural connectivity with cognition in each group. Hedges's effect size was used to compute the strength of associations. Results: We found a very low association between CRQ scores and connectivity metrics in PwMS-CP, while in PwMS-CI, this relation was low to moderate. The multiple regression model, adjusted for age, gender, mood, lesion volume, and graph metrics (local and global efficiency, and transitivity), indicated that the CRQ (β = 0.26, 95% CI: 0.17–0.35) was associated with cognition (adj R
2 = 0.34) in PwMS-CP (55%). In PwMS-CI, CRQ (β = 0.18, 95% CI: 0.07–0.29), age, and network global efficiency were independently associated with cognition (adj R2 = 0.55). The age- and gender-adjusted association between CRQ score and global efficiency on having an impaired cognitive status was −0.338 (OR: 0.71, p = 0.036) and −0.531 (OR: 0.59, p = 0.002), respectively. Conclusions: CR seems to have a marginally significant effect on brain structural connectivity, observed in patients with more severe clinical impairment. It protects PwMS from cognitive decline regardless of their cognitive status, yet once cognitive impairment has set in, brain damage and aging are also influencing cognitive performance. [ABSTRACT FROM AUTHOR]- Published
- 2020
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10. Retinal and brain damage during multiple sclerosis course: inflammatory activity is a key factor in the first 5 years.
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Pulido-Valdeolivas, Irene, Andorrà, Magí, Gómez-Andrés, David, Nakamura, Kunio, Alba-Arbalat, Salut, Lampert, Erika J., Zubizarreta, Irati, Llufriu, Sara, Martinez-Heras, Eloy, Solana, Elisabeth, Sola-Valls, Nuria, Sepulveda, María, Tercero-Uribe, Ana, Blanco, Yolanda, Camos-Carreras, Anna, Sanchez-Dalmau, Bernardo, Villoslada, Pablo, Saiz, Albert, and Martinez-Lapiscina, Elena H.
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BRAIN damage ,MULTIPLE sclerosis ,INFLAMMATION ,RETINAL ganglion cells ,GENETIC toxicology - Abstract
Understanding of the role of focal inflammation, a treatable feature, on neuro-axonal injury, is paramount to optimize neuroprotective strategy in MS. To quantify the impact of focal inflammatory activity on the rate of neuro-axonal injury over the MS course. We quantified the annualized rates of change in peripapillary retinal nerve fiber layer, ganglion cell plus inner plexiform layer (GCIPL), whole-brain, gray matter and thalamic volumes in patients with and without focal inflammatory activity in 161 patients followed over 5 years. We used mixed models including focal inflammatory activity (the presence of at least one relapse or a new/enlarging T2-FLAIR or gadolinium- enhancing lesion), and its interaction with time adjusted by age, sex, use of disease-modifying therapies and steroids, and prior optic neuritis. The increased rate of neuro-axonal injury during the first five years after onset was more prominent among active patients, as reflected by the changes in GCIPL thickness (p = 0.02), whole brain (p = 0.002) and thalamic volumes (p < 0.001). Thereafter, rates of retinal and brain changes stabilized and were similar in active and stable patients. Focal inflammatory activity is associated with neurodegeneration early in MS which reinforces the use of an early intensive anti-inflammatory therapy to prevent neurodegeneration in MS. [ABSTRACT FROM AUTHOR]
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- 2020
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11. Using Acute Optic Neuritis Trials to Assess Neuroprotective and Remyelinating Therapies in Multiple Sclerosis.
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Andorrà, Magí, Alba-Arbalat, Salut, Camos-Carreras, Anna, Gabilondo, Iñigo, Fraga-Pumar, Elena, Torres-Torres, Ruben, Pulido-Valdeolivas, Irene, Tercero-Uribe, Ana I., Guerrero-Zamora, Ana M., Ortiz-Perez, Santiago, Zubizarreta, Irati, Sola-Valls, Nuria, Llufriu, Sara, Sepulveda, Maria, Martinez-Hernandez, Eugenia, Armangue, Thais, Blanco, Yolanda, Villoslada, Pablo, Sanchez-Dalmau, Bernardo, and Saiz, Albert
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- 2020
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12. Modified connectivity of vulnerable brain nodes in multiple sclerosis, their impact on cognition and their discriminative value.
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Solana, Elisabeth, Martinez-Heras, Eloy, Casas-Roma, Jordi, Calvet, Laura, Lopez-Soley, Elisabet, Sepulveda, Maria, Sola-Valls, Nuria, Montejo, Carmen, Blanco, Yolanda, Pulido-Valdeolivas, Irene, Andorra, Magi, Saiz, Albert, Prados, Ferran, and Llufriu, Sara
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MULTIPLE sclerosis ,COGNITION ,VOLUNTEERS ,SUPPORT vector machines ,SOFTWARE measurement - Abstract
Brain structural network modifications in multiple sclerosis (MS) seem to be clinically relevant. The discriminative ability of those changes to identify MS patients or their cognitive status remains unknown. Therefore, this study aimed to investigate connectivity changes in MS patients related to their cognitive status, and to define an automatic classification method to classify subjects as patients and healthy volunteers (HV) or as cognitively preserved (CP) and impaired (CI) patients. We analysed structural brain connectivity in 45 HV and 188 MS patients (104 CP and 84 CI). A support vector machine with k-fold cross-validation was built using the graph metrics features that best differentiate the groups (p < 0.05). Local efficiency (LE) and node strength (NS) network properties showed the largest differences: 100% and 69.7% of nodes had reduced LE and NS in CP patients compared to HV. Moreover, 55.3% and 57.9% of nodes had decreased LE and NS in CI compared to CP patients, in associative multimodal areas. The classification method achieved an accuracy of 74.8–77.2% to differentiate patients from HV, and 59.9–60.8% to discriminate CI from CP patients. Structural network integrity is widely reduced and worsens as cognitive function declines. Central network properties of vulnerable nodes can be useful to classify MS patients. [ABSTRACT FROM AUTHOR]
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- 2019
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13. Late-onset neuromyelitis optica spectrum disorder: The importance of autoantibody serostatus.
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Sepulveda, Maria, Delgado-García, Guillermo, Blanco, Yolanda, Sola-Valls, Nuria, Martinez-Lapiscina, Elena H., Armangué, Thaís, Montejo, Carmen, Pulido-Valdeolivas, Irene, Martinez-Hernandez, Eugenia, Ariño, Helena, Escudero, Domingo, Ruiz-García, Raquel, Llufriu, Sara, Dalmau, Josep, Graus, Francesc, and Saiz, Albert
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- 2019
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14. Axonal and Myelin Neuroprotection by the Peptoid BN201 in Brain Inflammation.
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Villoslada, Pablo, Vila, Gemma, Colafrancesco, Valeria, Moreno, Beatriz, Fernandez-Diez, Begoña, Vazquez, Raquel, Pertsovskaya, Inna, Zubizarreta, Irati, Pulido-Valdeolivas, Irene, Messeguer, Joaquin, Vendrell-Navarro, Gloria, Frade, Jose Maria, López-Sánchez, Noelia, Teixido, Meritxell, Giralt, Ernest, Masso, Mar, Dugas, Jason C, Leonoudakis, Dmitri, Lariosa-Willingham, Karen D., and Steinman, Lawrence
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The development of neuroprotective therapies is a sought-after goal. By screening combinatorial chemical libraries using in vitro assays, we identified the small molecule BN201 that promotes the survival of cultured neural cells when subjected to oxidative stress or when deprived of trophic factors. Moreover, BN201 promotes neuronal differentiation, the differentiation of precursor cells to mature oligodendrocytes in vitro, and the myelination of new axons. BN201 modulates several kinases participating in the insulin growth factor 1 pathway including serum-glucocorticoid kinase and midkine, inducing the phosphorylation of NDRG1 and the translocation of the transcription factor Foxo3 to the cytoplasm. In vivo, BN201 prevents axonal and neuronal loss, and it promotes remyelination in models of multiple sclerosis, chemically induced demyelination, and glaucoma. In summary, we provide a new promising strategy to promote neuroaxonal survival and remyelination, potentially preventing disability in brain diseases. [ABSTRACT FROM AUTHOR]
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- 2019
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15. MAPK pathway and B cells overactivation in multiple sclerosis revealed by phosphoproteomics and genomic analysis.
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Kotelnikova, Ekaterina, Kiani, Narsis A., Messinis, Dimitris, Pertsovskaya, Inna, Pliaka, Vicky, Bernardo-Faura, Marti, Rinas, Melanie, Vila, Gemma, Zubizarreta, Irati, Pulido-Valdeolivas, Irene, Sakellaropoulos, Theodore, Faigle, Wolfgang, Silberberg, Gilad, Masso, Mar, Stridh, Pernilla, Behrens, Janina, Olsson, Tomas, Martin, Roland, Paul, Friedemann, and Alexopoulos, Leonidas G.
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PHOSPHORYLATION ,MULTIPLE sclerosis ,CELL proliferation ,IMMUNE response ,T cells ,GENE expression - Abstract
Dysregulation of signaling pathways in multiple sclerosis (MS) can be analyzed by phosphoproteomics in peripheral blood mononuclear cells (PBMCs). We performed in vitro kinetic assays on PBMCs in 195 MS patients and 60 matched controls and quantified the phosphorylation of 17 kinases using xMAP assays. Phosphopro- tein levels were tested for association with genetic susceptibility by typing 112 single-nucleotide polymorphisms (SNPs) associated with MS susceptibility. We found increased phosphorylation of MP2K1 in MS patients relative to the controls. Moreover, we identified one SNP located in the PHDGH gene and another on IRF8 gene that were associated with MP2K1 phosphorylation levels, providing a first clue on how this MS risk gene may act. The analyses in patients treated with disease-modifying drugs identified the phosphorylation of each receptor's downstream kinases. Finally, using flow cytometry, we detected in MS patients increased STAT1, STAT3, TF65, and HSPB1 phosphorylation in CD19
+ cells. These findings indicate the activation of cell survival and proliferation (MAPK), and proinflammatory (STAT) pathways in the immune cells of MS patients, primarily in B cells. The changes in the activation of these kinases suggest that these pathways may represent therapeutic targets for modulation by kinase inhibitors. [ABSTRACT FROM AUTHOR]- Published
- 2019
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16. Muscle imaging in laminopathies: Synthesis study identifies meaningful muscles for follow-up.
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GóMez‐Andrés, David, Díaz‐Manera, Jordi, Alejaldre, Aida, Pulido‐Valdeolivas, Irene, GonzáLez‐mera, Laura, Olivé, Montse, Vilchez, Juan José, De Munain, Adolfo LóPez, Paradas, Carmen, Muelas, Nuria, SáNchez‐MontáÑez, Ángel, Alonso‐Jimenez, Alicia, De la banda, Marta Gómez García, Dabaj, Ivana, Bonne, Gisèle, Munell, Francina, Carlier, Robert Y., Quijano‐Roy, Susana, GóMez-Andrés, David, and Díaz-Manera, Jordi
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Introduction: Particular fibroadipose infiltration patterns have been recently described by muscle imaging in congenital and later onset forms of LMNA-related muscular dystrophies (LMNA-RD).Methods: Scores for fibroadipose infiltration of 23 lower limb muscles in 34 patients with LMNA-RD were collected from heat maps of 2 previous studies. Scoring systems were homogenized. Relationships between muscle infiltration and disease duration and age of onset were modeled with random forests.Results: The pattern of infiltration differs according to disease duration but not to age of disease onset. The muscles whose progression best predicts disease duration were semitendinosus, biceps femoris long head, gluteus medius, and semimembranosus.Discussion: In LMNA-RD, our synthetic analysis of lower limb muscle infiltration did not find major differences between forms with different ages of onset but allowed the identification of muscles with characteristic infiltration during disease progression. Monitoring of these specific muscles by quantitative MRI may provide useful imaging biomarkers in LMNA-RD. Muscle Nerve 58:812-817, 2018. [ABSTRACT FROM AUTHOR]- Published
- 2018
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17. Assessing Biological and Methodological Aspects of Brain Volume Loss in Multiple Sclerosis.
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Andorra, Magí, Nakamura, Kunio, Lampert, Erika J., Pulido-Valdeolivas, Irene, Zubizarreta, Irati, Llufriu, Sara, Martinez-Heras, Eloy, Sola-Valls, Nuria, Sepulveda, María, Tercero-Uribe, Ana, Blanco, Yolanda, Saiz, Albert, Villoslada, Pablo, and Martinez-Lapiscina, Elena H.
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- 2018
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18. Early retinal atrophy predicts long-term visual impairment after acute optic neuritis.
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Sanchez-Dalmau, Bernardo, Martinez-Lapiscina, Elena H., Torres-Torres, Ruben, Ortiz-Perez, Santiago, Zubizarreta, Irati, Pulido-Valdeolivas, Irene V., Alba-Arbalat, Salut, Guerrero-Zamora, Ana, Calbet, David, and Villoslada, Pablo
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OPTIC neuritis ,NEUROMYELITIS optica ,VISUAL acuity ,COLOR vision ,VISION disorders - Abstract
Background: Visual recovery after optic neuritis (ON) used to be defined as good, although patients frequently complain of poor vision. Methods: We carried out a prospective study on 38 consecutive patients with acute ON followed monthly for 6 months and evaluated high- and low-contrast visual acuity (HCVA and LCVA, respectively), quality of vision (National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25)), visual fields, and retinal thickness by spectral domain optical coherence tomography (OCT). Results: We found significant impaired LCVA and color vision in ON eyes 6 months after acute ON, which impact on quality of life. LCVA and color vision were correlated with the thicknesses of the ganglion cell and inner plexiform layer (GCIPL; 2.5% LCVA r = 0.65 and p = 0.0001; color vision r = 0.75 and p < 0.0001) and that of the peripapillary retinal nerve fiber layer (pRNFL; LCVA r = 0.43 and p = 0.0098; color vision r = 0.62 and p < 0.0001). Linear regression models that included the change in the GCIPL and pRNFL thicknesses from baseline to month 1 after onset explained 47% of the change in 2.5% LCVA and 67% of the change of color vision acuity. When adjusting for the value of visual acuity at baseline, predictors of the change in vision from baseline to month 6 achieved similar performance for all three types of vision (HCVA, LCVA, and color vision). Conclusion: Monitoring retinal atrophy by OCT within the first month after ON onset allows individuals at a high risk of residual visual impairment to be identified. [ABSTRACT FROM AUTHOR]
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- 2018
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19. Predictors of vision impairment in Multiple Sclerosis.
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Sanchez-Dalmau, Bernardo, Martinez-Lapiscina, Elena H., Pulido-Valdeolivas, Irene, Zubizarreta, Irati, Llufriu, Sara, Blanco, Yolanda, Sola-Valls, Nuria, Sepulveda, Maria, Guerrero, Ana, Alba, Salut, Andorra, Magi, Camos, Anna, Sanchez-Vela, Laura, Alfonso, Veronica, Saiz, Albert, and Villoslada, Pablo
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VISION disorders ,MULTIPLE sclerosis ,QUALITY of life ,COLOR vision ,OPTICAL coherence tomography ,PATIENTS - Abstract
Visual impairment significantly alters the quality of life of people with Multiple Sclerosis (MS). The objective of this study was to identify predictors (independent variables) of visual outcomes, and to define their relationship with neurological disability and retinal atrophy when assessed by optical coherence tomography (OCT). We performed a cross-sectional analysis of 119 consecutive patients with MS, assessing vision using high contrast visual acuity (LogMar), 2.5% and 1.25% low contrast visual acuity (Sloan charts), and color vision (Hardy-Rand-Rittler plates). Quality of vision is a patient reported outcome based on an individual's unique perception of his or her vision and was assessed with the Visual Functioning Questionnaire-25 (VFQ-25) with the 10 neuro-ophthalmologic items. MS disability was assessed using the expanded disability status scale (EDSS), the MS functional composite (MSFC) and the brief repetitive battery-neuropsychology (BRB-N). Retinal atrophy was assessed using spectral domain OCT, measuring the thickness of the peripapillar retinal nerve fiber layer (pRNFL) and the volume of the ganglion cell plus inner plexiform layer (GCIPL). The vision of patients with MS was impaired, particularly in eyes with prior optic neuritis. Retinal atrophy (pRNFL and GCIPL) was closely associated with impaired low contrast vision and color vision, whereas the volume of the GCIPL showed a trend (p = 0.092) to be associated with quality of vision. Multiple regression analysis revealed that EDSS was an explanatory variable for high contrast vision after stepwise analysis, GCIPL volume for low contrast vision, and GCIPL volume and EDSS for color vision. The explanatory variables for quality of vision were high contrast vision and color vision. In summary, quality of vision in MS depends on the impairment of high contrast visual acuity and color vision due to the disease. [ABSTRACT FROM AUTHOR]
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- 2018
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20. Gait phenotypes in paediatric hereditary spastic paraplegia revealed by dynamic time warping analysis and random forests.
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Pulido-Valdeolivas, Irene, Gómez-Andrés, David, Martín-Gonzalo, Juan Andrés, Rodríguez-Andonaegui, Irene, López-López, Javier, Pascual-Pascual, Samuel Ignacio, and Rausell, Estrella
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FAMILIAL spastic paraplegia ,EVOKED potentials (Electrophysiology) ,PHENOTYPES ,RANDOM forest algorithms ,HIERARCHICAL clustering (Cluster analysis) ,THERAPEUTICS - Abstract
The Hereditary Spastic Paraplegias (HSP) are a group of heterogeneous disorders with a wide spectrum of underlying neural pathology, and hence HSP patients express a variety of gait abnormalities. Classification of these phenotypes may help in monitoring disease progression and personalizing therapies. This is currently managed by measuring values of some kinematic and spatio-temporal parameters at certain moments during the gait cycle, either in the doctor´s surgery room or after very precise measurements produced by instrumental gait analysis (IGA). These methods, however, do not provide information about the whole structure of the gait cycle. Classification of the similarities among time series of IGA measured values of sagittal joint positions throughout the whole gait cycle can be achieved by hierarchical clustering analysis based on multivariate dynamic time warping (DTW). Random forests can estimate which are the most important isolated parameters to predict the classification revealed by DTW, since clinicians need to refer to them in their daily practice. We acquired time series of pelvic, hip, knee, ankle and forefoot sagittal angular positions from 26 HSP and 33 healthy children with an optokinetic IGA system. DTW revealed six gait patterns with different degrees of impairment of walking speed, cadence and gait cycle distribution and related with patient’s age, sex, GMFCS stage, concurrence of polyneuropathy and abnormal visual evoked potentials or corpus callosum. The most important parameters to differentiate patterns were mean pelvic tilt and hip flexion at initial contact. Longer time of support, decreased values of hip extension and increased knee flexion at initial contact can differentiate the mildest, near to normal HSP gait phenotype and the normal healthy one. Increased values of knee flexion at initial contact and delayed peak of knee flexion are important factors to distinguish GMFCS stages I from II-III and concurrence of polyneuropathy. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
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21. Combined walking outcome measures identify clinically meaningful response to prolonged-release fampridine.
- Author
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Sola-Valls, Núria, Blanco, Yolanda, Sepúlveda, María, Llufriu, Sara, Martínez-Lapiscina, Elena H., Zubizarreta, Irati, Pulido-Valdeolivas, Irene, Montejo, Carmen, Villoslada, Pablo, and Saiz, Albert
- Abstract
Background: Gait impairment is common in multiple sclerosis (MS) and negatively impacts patients’ health-related quality of life (HRQoL). Prolonged-release fampridine (PR-fam) improves walking speed, but it is unclear which walking measures are the most suitable for identifying treatment response. Our aim was to assess the effect of PR-fam and the outcome measures that best identify short- and long-term clinically meaningful response. Methods: We conducted a prospective study in 32 MS patients treated with PR-fam for a year. The assessments at 2 weeks, 3, 6 and 12 months included: timed 25-foot walk (T25FW), 6-minute walk test (6MWT), MS Walking Scale-12 (MSWS-12), a five-level version of the EuroQoL-5 dimensions, and accelerometry. PR-fam response was defined as an improvement in T25FW ⩾20%. Results: Twenty-five (78%) patients were considered responders after 2 weeks of PR-fam and improved significantly in all measures. Responders to T25FW and MSWS-12 (n = 19) showed a significant improvement in HRQoL and accelerometer data compared with responders only to T25FW (n = 6). At 1 year, 15/20 (75%) patients remained responders, but only those with permanent response to T25FW and MSWS-12 (n = 8; 53%) showed a significant improvement in 6MWT and HRQoL. Conclusion: The combination of T25FW and MSWS-12 identify better those patients with a clinically significant benefit of PR-fam. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
22. Characterizing Normal and Pathological Gait through Permutation Entropy.
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Zanin, Massimiliano, Gómez-Andrés, David, Pulido-Valdeolivas, Irene, Martín-Gonzalo, Juan Andrés, López-López, Javier, Pascual-Pascual, Samuel Ignacio, and Rausell, Estrella
- Subjects
GAIT in humans ,CEREBRAL palsy ,BRAIN damage ,NEURAL circuitry ,DISABILITIES - Abstract
Cerebral palsy is a physical impairment stemming from a brain lesion at perinatal time, most of the time resulting in gait abnormalities: the first cause of severe disability in childhood. Gait study, and instrumental gait analysis in particular, has been receiving increasing attention in the last few years, for being the complex result of the interactions between different brain motor areas and thus a proxy in the understanding of the underlying neural dynamics. Yet, and in spite of its importance, little is still known about how the brain adapts to cerebral palsy and to its impaired gait and, consequently, about the best strategies for mitigating the disability. In this contribution, we present the hitherto first analysis of joint kinematics data using permutation entropy, comparing cerebral palsy children with a set of matched control subjects. We find a significant increase in the permutation entropy for the former group, thus indicating a more complex and erratic neural control of joints and a non-trivial relationship between the permutation entropy and the gait speed. We further show how this information theory measure can be used to train a data mining model able to forecast the child's condition. We finally discuss the relevance of these results in clinical applications and specifically in the design of personalized medicine interventions. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
23. Dynamics and heterogeneity of brain damage in multiple sclerosis.
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Kotelnikova, Ekaterina, Kiani, Narsis A., Abad, Elena, Martinez-Lapiscina, Elena H., Andorra, Magi, Zubizarreta, Irati, Pulido-Valdeolivas, Irene, Pertsovskaya, Inna, Alexopoulos, Leonidas G., Olsson, Tomas, Martin, Roland, Paul, Friedemann, Tegnér, Jesper, Garcia-Ojalvo, Jordi, and Villoslada, Pablo
- Subjects
MULTIPLE sclerosis ,BRAIN damage ,INFLAMMATION ,NEURODEGENERATION ,MYELINATION ,AXONS ,NEUROPHYSIOLOGY ,MATHEMATICAL models - Abstract
Multiple Sclerosis (MS) is an autoimmune disease driving inflammatory and degenerative processes that damage the central nervous system (CNS). However, it is not well understood how these events interact and evolve to evoke such a highly dynamic and heterogeneous disease. We established a hypothesis whereby the variability in the course of MS is driven by the very same pathogenic mechanisms responsible for the disease, the autoimmune attack on the CNS that leads to chronic inflammation, neuroaxonal degeneration and remyelination. We propose that each of these processes acts more or less severely and at different times in each of the clinical subgroups. To test this hypothesis, we developed a mathematical model that was constrained by experimental data (the expanded disability status scale [EDSS] time series) obtained from a retrospective longitudinal cohort of 66 MS patients with a long-term follow-up (up to 20 years). Moreover, we validated this model in a second prospective cohort of 120 MS patients with a three-year follow-up, for which EDSS data and brain volume time series were available. The clinical heterogeneity in the datasets was reduced by grouping the EDSS time series using an unsupervised clustering analysis. We found that by adjusting certain parameters, albeit within their biological range, the mathematical model reproduced the different disease courses, supporting the dynamic CNS damage hypothesis to explain MS heterogeneity. Our analysis suggests that the irreversible axon degeneration produced in the early stages of progressive MS is mainly due to the higher rate of myelinated axon degeneration, coupled to the lower capacity for remyelination. However, and in agreement with recent pathological studies, degeneration of chronically demyelinated axons is not a key feature that distinguishes this phenotype. Moreover, the model reveals that lower rates of axon degeneration and more rapid remyelination make relapsing MS more resilient than the progressive subtype. Therefore, our results support the hypothesis of a common pathogenesis for the different MS subtypes, even in the presence of genetic and environmental heterogeneity. Hence, MS can be considered as a single disease in which specific dynamics can provoke a variety of clinical outcomes in different patient groups. These results have important implications for the design of therapeutic interventions for MS at different stages of the disease. [ABSTRACT FROM AUTHOR]
- Published
- 2017
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24. Metabolomic signatures associated with disease severity in multiple sclerosis.
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Villoslada, Pablo, Alonso, Cristina, Agirrezabal, Ion, Kotelnikova, Ekaterina, Zubizarreta, Irati, Pulido-Valdeolivas, Irene, Saiz, Albert, Comabella, Manuel, Montalban, Xavier, Villar, Luisa, Alvarez-Cermeño, Jose Carlos, Fernández, Oscar, Alvarez-Lafuente, Roberto, Arroyo, Rafael, and Castro, Azucena
- Published
- 2017
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25. Patterns of motor signs in spinocerebellar ataxia type 3 at the start of follow-up in a reference unit.
- Author
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Pulido-Valdeolivas, Irene, Gómez-Andrés, David, Sanz-Gallego, Irene, Rausell, Estrella, and Arpa, Javier
- Published
- 2016
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26. Substantia Nigra Echogenicity in Hereditary Ataxias With and Without Nigrostriatal Pathology: a Pilot Study.
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Martínez-Sánchez, Patricia, Cazorla-García, Rubén, Sanz-Gallego, Irene, Correas-Callero, Elisa, Pulido-Valdeolivas, Irene, and Arpa, Javier
- Subjects
FRIEDREICH'S ataxia ,SUBSTANTIA nigra ,SPINOCEREBELLAR ataxia ,BRAIN imaging ,ULTRASONIC imaging ,MEDICAL research - Abstract
Our objective was to determine whether substantia nigra (SN) hyperechogenicity is greater in spinocerebellar ataxias (SCA) with nigrostriatal affectation than in ataxias without it. A cross-sectional case-control study analyzing four groups of patients was conducted: 1) nigrostriatal ataxias (SCA3 and SCA6), 2) nigrostriatal healthy controls matched by age and sex, 3) non-nigrostriatal ataxias (FRDA and SCA7), and 4) non-nigrostriatal healthy controls matched by age and sex. All the patients underwent a transcranial ultrasound performed by an experienced sonographer blinded to the clinical, genetic, and neuroimaging data. The SN area was measured and compared in the four groups. The SN area was also correlated with clinical features and genetic data in the two ataxia groups. We examined 12 patients with nigrostriatal ataxia (11 SCA3 and 1 SCA6), 12 nigrostriatal healthy control patients, 7 patients with non-nigrostriatal ataxia (5 FRDA and 2 SCA7), and 7 non-nigrostriatal healthy control patients. The median (IQR) SN area (cm) was greater in the nigrostriatal ataxias compared with the controls (right SN, 0.43 [0.44] vs. 0.11 [0.25]; P = 0.001; left SN, 0.32 [0.25] vs. 0.11 [0.16]; P = 0.001), but was similar among the non-nigrostriatal ataxias and controls. There were no statistically significant differences in the SN area between the nigrostriatal and non-nigrostriatal ataxias, although there was a tendency for a greater left SN area in the nigrostriatal compared with the non-nigrostriatal ataxias (0.32 [0.25] vs. 0.16 [0.24], P = 0.083). SN echogenicity is markedly greater in ataxias with nigrostriatal pathology than in controls. The role of SN hyperechogenicity in differentiating ataxias with and without nigrostriatal pathology should be elucidated in future studies. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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27. Abnormal Motor Phenotype at Adult Stages in Mice Lacking Type 2 Deiodinase.
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Bárez-López, Soledad, Bosch-García, Daniel, Gómez-Andrés, David, Pulido-Valdeolivas, Irene, Montero-Pedrazuela, Ana, Obregon, Maria Jesus, and Guadaño-Ferraz, Ana
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PHENOTYPES ,MOTOR ability ,LABORATORY mice ,IODIDE peroxidase ,THYROID hormones ,CENTRAL nervous system physiology ,SKELETAL muscle - Abstract
Background: Thyroid hormones have a key role in both the developing and adult central nervous system and skeletal muscle. The thyroid gland produces mainly thyroxine (T4) but the intracellular concentrations of 3,5,3′-triiodothyronine (T3; the transcriptionally active hormone) in the central nervous system and skeletal muscle are modulated by the activity of type 2 deiodinase (D2). To date no neurological syndrome has been associated with mutations in the DIO2 gene and previous studies in young and juvenile D2-knockout mice (D2KO) did not find gross neurological alterations, possibly due to compensatory mechanisms. Aim: This study aims to analyze the motor phenotype of 3-and-6-month-old D2KO mice to evaluate the role of D2 on the motor system at adult stages in which compensatory mechanisms could have failed. Results: Motor abilities were explored by validated tests. In the footprint test, D2KO showed an altered global gait pattern (mice walked slower, with shorter strides and with a hindlimb wider base of support than wild-type mice). No differences were detected in the balance beam test. However, a reduced latency to fall was found in the rotarod, coat-hanger and four limb hanging wire tests indicating impairment on coordination and prehensile reflex and a reduction of muscle strength. In histological analyses of cerebellum and skeletal muscle, D2KO mice did not present gross structural abnormalities. Thyroid hormones levels and deiodinases activities were also determined. In D2KO mice, despite euthyroid T3 and high T4 plasma levels, T3 levels were significantly reduced in cerebral cortex (48% reduction) and skeletal muscle (33% reduction), but not in the cerebellum where other deiodinase (type 1) is expressed. Conclusions: The motor alterations observed in D2KO mice indicate an important role for D2 in T3 availability to maintain motor function and muscle strength. Our results suggest a possible implication of D2 in motor disorders. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
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28. Dynamics and Predictors of Cognitive Impairment along the Disease Course in Multiple Sclerosis.
- Author
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Lopez-Soley, Elisabet, Martinez-Heras, Eloy, Andorra, Magi, Solanes, Aleix, Radua, Joaquim, Montejo, Carmen, Alba-Arbalat, Salut, Sola-Valls, Nuria, Pulido-Valdeolivas, Irene, Sepulveda, Maria, Romero-Pinel, Lucia, Munteis, Elvira, Martínez-Rodríguez, Jose E., Blanco, Yolanda, Martinez-Lapiscina, Elena H., Villoslada, Pablo, Saiz, Albert, Solana, Elisabeth, and Llufriu, Sara
- Subjects
MULTIPLE sclerosis ,DISEASE progression ,COGNITION disorders ,VERBAL memory ,COGNITION ,CINGULATE cortex - Abstract
(1) Background: The evolution and predictors of cognitive impairment (CI) in multiple sclerosis (MS) are poorly understood. We aimed to define the temporal dynamics of cognition throughout the disease course and identify clinical and neuroimaging measures that predict CI. (2) Methods: This paper features a longitudinal study with 212 patients who underwent several cognitive examinations at different time points. Dynamics of cognition were assessed using mixed-effects linear spline models. Machine learning techniques were used to identify which baseline demographic, clinical, and neuroimaging measures best predicted CI. (3) Results: In the first 5 years of MS, we detected an increase in the z-scores of global cognition, verbal memory, and information processing speed, which was followed by a decline in global cognition and memory (p < 0.05) between years 5 and 15. From 15 to 30 years of disease onset, cognitive decline continued, affecting global cognition and verbal memory. The baseline measures that best predicted CI were education, disease severity, lesion burden, and hippocampus and anterior cingulate cortex volume. (4) Conclusions: In MS, cognition deteriorates 5 years after disease onset, declining steadily over the next 25 years and more markedly affecting verbal memory. Education, disease severity, lesion burden, and volume of limbic structures predict future CI and may be helpful when identifying at-risk patients. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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29. Permutation Entropy and Irreversibility in Gait Kinematic Time Series from Patients with Mild Cognitive Decline and Early Alzheimer's Dementia.
- Author
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Martín-Gonzalo, Juan-Andrés, Pulido-Valdeolivas, Irene, Wang, Yu, Wang, Ting, Chiclana-Actis, Guadalupe, Algarra-Lucas, Maria del Carmen, Palmí-Cortés, Itziar, Fernández Travieso, Jorge, Torrecillas-Narváez, Maria Dolores, Miralles-Martinez, Ambrosio A., Rausell, Estrella, Gómez-Andrés, David, and Zanin, Massimiliano
- Subjects
ALZHEIMER'S disease ,TIME series analysis ,AGE factors in cognition disorders ,MILD cognitive impairment ,PERMUTATIONS ,ENTROPY - Abstract
Gait is a basic cognitive purposeful action that has been shown to be altered in late stages of neurodegenerative dementias. Nevertheless, alterations are less clear in mild forms of dementia, and the potential use of gait analysis as a biomarker of initial cognitive decline has hitherto mostly been neglected. Herein, we report the results of a study of gait kinematic time series for two groups of patients (mild cognitive impairment and mild Alzheimer's disease) and a group of matched control subjects. Two metrics based on permutation patterns are considered, respectively measuring the complexity and irreversibility of the time series. Results indicate that kinematic disorganisation is present in early phases of cognitive impairment; in addition, they depict a rich scenario, in which some joint movements display an increased complexity and irreversibility, while others a marked decrease. Beyond their potential use as biomarkers, complexity and irreversibility metrics can open a new door to the understanding of the role of the nervous system in gait, as well as its adaptation and compensatory mechanisms. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
30. Putamina Involvement in Wernicke Encephalopathy Induced by Janus Kinase 2 Inhibitor.
- Author
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Rodríguez-Pardo, Jorge, Puertas-Muñoz, Inmaculada, Martínez-Sánchez, Patricia, de Terán, Javier Díaz, Pulido-Valdeolivas, Irene, and Fuentes, Blanca
- Published
- 2015
- Full Text
- View/download PDF
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