المؤلفون: Gil-Varea, Elia, Urcelay, Elena, Vilariño-Güell, Carles, Costa, Carme, Midaglia, Luciana, Matesanz, Fuencisla, Rodríguez-Antigüedad, Alfredo, Oksenberg, Jorge, Espino-Paisan, Laura, Dessa Sadovnick, A, Saiz, Albert, Villar, Luisa M, García-Merino, Juan Antonio, Ramió-Torrentà, Lluís, Triviño, Juan Carlos, Quintana, Ester, Robles, René, Sánchez-López, Antonio, Arroyo, Rafael, Alvarez-Cermeño, Jose C, Vidal-Jordana, Angela, Malhotra, Sunny, Fissolo, Nicolas, Montalban, Xavier, Comabella, Manuel

المصدر: Journal of Neuroinflammation. 15(1)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Neurosciences, Immunology, Autoimmune Disease, Human Genome, Multiple Sclerosis, Neurodegenerative, Genetics, Brain Disorders, Clinical Research, 4.2 Evaluation of markers and technologies, Detection, screening and diagnosis, Aetiology, 2.1 Biological and endogenous factors, Neurological, Brain, Carboxypeptidases A, Cohort Studies, Disease Progression, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Immunoglobulins, Male, Nerve Tissue Proteins, Polymorphism, Single Nucleotide, RNA, Messenger, Exome Sequencing, Multiple sclerosis, Disease course, Exome sequencing, Polymorphisms, CPXM2, IGSF9B, NLRP9, Clinical Sciences, Neurology & Neurosurgery

الوصف: BackgroundIt remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients.MethodsMS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies.ResultsBy means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/6w7000xbTest

المؤلفون: Marti-Juan, Gerard, Sastre-Garriga, Jaume, Martinez-Heras, Eloy, Vidal-Jordana, Angela, Llufriu, Sara, Groppa, Sergiu, Gonzalez-Escamilla, Gabriel, Rocca, Maria A, Filippi, Massimo, Hogestol, Einar A, Harbo, Hanne F, Foster, Michael A, Toosy, Ahmed T, Schoonheim, Menno M, Tewarie, Prejaas, Pontillo, Giuseppe, Petracca, Maria, Rovira, Alex, Deco, Gustavo, Pareto, Deborah

المصدر: Cerebral Cortex , 33 (12) pp. 7322-7334. (2023)

مصطلحات موضوعية: CONSENSUS RECOMMENDATIONS, DEMYELINATION, DIFFUSION MRI, functional connectivity, IMPLEMENTATION, INTEGRATION, LARGE-SCALE BRAIN, Life Sciences & Biomedicine, MATTER, MRI, multiple sclerosis, Neurosciences, Neurosciences & Neurology, RECONSTRUCTION, REPRODUCIBILITY, Science & Technology, structural connectivity, The Virtual Brain, TRACTOGRAPHY

الوصف: The relationship between structural connectivity (SC) and functional connectivity (FC) captured from magnetic resonance imaging, as well as its interaction with disability and cognitive impairment, is not well understood in people with multiple sclerosis (pwMS). The Virtual Brain (TVB) is an open-source brain simulator for creating personalized brain models using SC and FC. The aim of this study was to explore SC-FC relationship in MS using TVB. Two different model regimes have been studied: stable and oscillatory, with the latter including conduction delays in the brain. The models were applied to 513 pwMS and 208 healthy controls (HC) from 7 different centers. Models were analyzed using structural damage, global diffusion properties, clinical disability, cognitive scores, and graph-derived metrics from both simulated and empirical FC. For the stable model, higher SC-FC coupling was associated with pwMS with low Single Digit Modalities Test (SDMT) score (F=3.48, P$\lt$0.05), suggesting that cognitive impairment in pwMS is associated with a higher SC-FC coupling. Differences in entropy of the simulated FC between HC, high and low SDMT groups (F=31.57, P$\lt$1e-5), show that the model captures subtle differences not detected in the empirical FC, suggesting the existence of compensatory and maladaptive mechanisms between SC and FC in MS.

وصف الملف: text

العلاقة: https://discovery.ucl.ac.uk/id/eprint/10171998/1/Toosy_TVB_Manuscript_Latex.pdfTest; https://discovery.ucl.ac.uk/id/eprint/10171998Test/

الإتاحة: https://discovery.ucl.ac.uk/id/eprint/10171998/1/Toosy_TVB_Manuscript_Latex.pdfTest
https://discovery.ucl.ac.uk/id/eprint/10171998Test/

المؤلفون: Gil Varea, Elia, Urcelay, Elena, Vilariño-Güell, Carles, Costa, Carme, Midaglia, Luciana, Matesanz, Fuencisla, Rodríguez-Antigüedad, Alfredo, Oksenberg, Jorge, Espino-Paisan, Laura, Dessa Sadovnick, A., Saiz, Albert, Villar, Luisa M., García-Merino, Juan Antonio, Ramió-Torrentà, Lluís, Triviño, Juan Carlos, Quintana, Ester, Robles, René, Sánchez-López, Antonio, Arroyo, Rafael, Alvarez-Cermeño, José C, Vidal-Jordana, Angela, Malhotra, Sunny, Fissolo, Nicolás, Montalban, Xavier, Comabella, Manuel, Universitat Autònoma de Barcelona

المساهمون: Instituto de Salud Carlos III, Junta de Andalucía, Ministerio de Economía y Competitividad (España), Society of Canada Scientific Research Foundation, European Commission, Canadian Institutes of Health Research

المصدر: Repositorio Institucional de la Consejería de Sanidad de la Comunidad de Madrid
Consejería de Sanidad de la Comunidad de Madrid
Dipòsit Digital de la UB
Universidad de Barcelona
Journal of Neuroinflammation, Vol 15, Iss 1, Pp 1-10 (2018)
Digital.CSIC. Repositorio Institucional del CSIC
instname
Dipòsit Digital de Documents de la UAB
Universitat Autònoma de Barcelona
Journal of neuroinflammation, vol 15, iss 1

مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, Exome sequencing, Carboxypeptidases A, Messenger, Esclerosi múltiple, Disease, Neurodegenerative, lcsh:RC346-429, Whole Exome Sequencing, Cohort Studies, Gene Frequency, 2.1 Biological and endogenous factors, Immunologia, Aetiology, IGSF9B, Disease course, screening and diagnosis, CPXM2, General Neuroscience, Brain, Single Nucleotide, Fenotip, Detection, Phenotype, Neurology, Neurological, Cohort, Disease Progression, Female, 4.2 Evaluation of markers and technologies, medicine.medical_specialty, Genotype, Clinical Sciences, Immunology, Immunoglobulins, NLRP9, Nerve Tissue Proteins, Single-nucleotide polymorphism, Autoimmune Disease, Polymorphism, Single Nucleotide, Multiple sclerosis, 03 medical and health sciences, Cellular and Molecular Neuroscience, Clinical Research, Internal medicine, Genetics, medicine, Humans, SNP, Genetic Predisposition to Disease, RNA, Messenger, Polymorphism, Genotyping, Allele frequency, lcsh:Neurology. Diseases of the nervous system, Neurology & Neurosurgery, business.industry, Human Genome, Neurosciences, medicine.disease, Brain Disorders, 030104 developmental biology, RNA, business, Polymorphisms

الوصف: [Background]: It remains unclear whether disease course in multiple sclerosis (MS) is influenced by genetic polymorphisms. Here, we aimed to identify genetic variants associated with benign and aggressive disease courses in MS patients.
[Methods]: MS patients were classified into benign and aggressive phenotypes according to clinical criteria. We performed exome sequencing in a discovery cohort, which included 20 MS patients, 10 with benign and 10 with aggressive disease course, and genotyping in 2 independent validation cohorts. The first validation cohort encompassed 194 MS patients, 107 with benign and 87 with aggressive phenotypes. The second validation cohort comprised 257 patients, of whom 224 patients had benign phenotypes and 33 aggressive disease courses. Brain immunohistochemistries were performed using disease course associated genes antibodies.
[Results]: By means of single-nucleotide polymorphism (SNP) detection and comparison of allele frequencies between patients with benign and aggressive phenotypes, a total of 16 SNPs were selected for validation from the exome sequencing data in the discovery cohort. Meta-analysis of genotyping results in two validation cohorts revealed two polymorphisms, rs28469012 and rs10894768, significantly associated with disease course. SNP rs28469012 is located in CPXM2 (carboxypeptidase X, M14 family, member 2) and was associated with aggressive disease course (uncorrected p value
[Conclusions]: Genetic variants located in CPXM2, IGSF9B, and NLRP9 have the potential to modulate disease course in MS patients and may be used as disease activity biomarkers to identify patients with divergent disease courses. Altogether, the reported results from this study support the influence of genetic factors in MS disease course and may help to better understand the complex molecular mechanisms underlying disease pathogenesis.
This work was supported by (a) grants PI10/02099, FIS PI13/0879, PI15/00513, PI15/00587, PI16/01259, RD16/0015/0001, RD16/0015/0002, RD16/0015/0004 integrated in the Plan Estatal de Investigación Científica y Técnica de Innovación I+D+I and co-funded by the Instituto de Salud Carlos IIISubdirección General de Evaluación and the Fondo Europeo de Desarrollo Regional (FEDER), and Red Española de Esclerosis Múltiple (REEM); (b) Junta de Andalucía (JA)-FEDER grant CTS2704, Ministerio de Economía y Competitividad (grant number SAF 2016-80595-C2-1-P); (c) MS Society of Canada Scientific Research Foundation as part of the CCPGSMS, and research undertaken thanks to funding from the Canada Research Chair (950-228408) program, Michael Smith Foundation for Health Research (16827) and Canadian Institutes of Health Research (MOP-137051).

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::42f07acfa9ee177bd2cea197dec7c791Test
http://hdl.handle.net/2445/157847Test

المؤلفون: Okuda, Darin T., Siva, Aksel, Kantarci, Orhun, Inglese, Matilde, Katz, Ilana, Tutuncu, Melih, Keegan, B. Mark, Donlon, Stacy, Hua, Le H., Vidal-Jordana, Angela, Montalban, Xavier, Rovira, Alex, Tintoré, Mar, Amato, Maria Pia, Brochet, Bruno, de Seze, Jérôme, Brassat, David, Vermersch, Patrick, De Stefano, Nicola, Sormani, Maria Pia

المصدر: PLoS ONE; Mar2014, Vol. 9 Issue 3, p1-9, 9p

مصطلحات موضوعية: MEDICAL radiology, MEDICAL databases, MULTIVARIATE analysis, MAGNETIC resonance imaging of the brain, NEUROSCIENCES, AUTOIMMUNE diseases, SPINAL cord

مستخلص: Objective: To report the 5-year risk and to identify risk factors for the development of a seminal acute or progressive clinical event in a multi-national cohort of asymptomatic subjects meeting 2009 RIS Criteria. Methods: Retrospectively identified RIS subjects from 22 databases within 5 countries were evaluated. Time to the first clinical event related to demyelination (acute or 12-month progression of neurological deficits) was compared across different groups by univariate and multivariate analyses utilizing a Cox regression model. Results: Data were available in 451 RIS subjects (F: 354 (78.5%)). The mean age at from the time of the first brain MRI revealing anomalies suggestive of MS was 37.2 years (y) (median: 37.1 y, range: 11–74 y) with mean clinical follow-up time of 4.4 y (median: 2.8 y, range: 0.01–21.1 y). Clinical events were identified in 34% (standard error = 3%) of individuals within a 5-year period from the first brain MRI study. Of those who developed symptoms, 9.6% fulfilled criteria for primary progressive MS. In the multivariate model, age [hazard ratio (HR): 0.98 (95% CI: 0.96–0.99); p = 0.03], sex (male) [HR: 1.93 (1.24–2.99); p = 0.004], and lesions within the cervical or thoracic spinal cord [HR: 3.08 (2.06–4.62); p = <0.001] were identified as significant predictors for the development of a first clinical event. Interpretation: These data provide supportive evidence that a meaningful number of RIS subjects evolve to a first clinical symptom. An age <37 y, male sex, and spinal cord involvement appear to be the most important independent predictors of symptom onset. [ABSTRACT FROM AUTHOR]

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المؤلفون: Patil, Sachi A.¹ (AUTHOR), Joseph, Binu² (AUTHOR), Tagliani, Paula³ (AUTHOR), Sastre-Garriga, Jaume³ (AUTHOR), Montalban, Xavier³ (AUTHOR), Vidal-Jordana, Angela³ (AUTHOR), Galetta, Steven L.^1,2 (AUTHOR), Balcer, Laura J.^1,2,4 (AUTHOR) laura.balcer@nyulangone.org, Kenney, Rachel C.^2,4,5,6 (AUTHOR)

المصدر: Journal of the Neurological Sciences. Oct2023, Vol. 453, pN.PAG-N.PAG. 1p.

مصطلحات موضوعية: *OPTICAL coherence tomography, *OPTIC nerve, *NEUROSCIENCES, *MULTIPLE sclerosis, *OPTIC neuritis