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Article: Time to rethink the reported disease-modifying treatment effects on cognitive outcomes: Methods and interpretative caveats.

Labiano-Fontcuberta, Andrés / Monreal, Enric / Benito-León, Julián

2022 Volume 13, Page(s) 995690

Language	English
Publishing date	2022-09-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2022.995690
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Article ; Online: Passive assessment of tapping speed through smartphone is useful for monitoring multiple sclerosis.

Chico-Garcia, Juan Luis / Sainz-Amo, Raquel / Monreal, Enric / Rodriguez-Jorge, Fernando / Sainz de la Maza, Susana / Masjuan, Jaime / Villar, Luisa María / Costa-Frossard França, Lucienne

Multiple sclerosis and related disorders

2024 Volume 86, Page(s) 105595

Abstract: Introduction: Continuously acquired smartphone keyboard interactions may be useful to monitor progression in multiple sclerosis (MS). We aimed to study the correlation between tapping speed (TS), measured as keys/s, and baseline disability scales in ... ...

Abstract	Introduction: Continuously acquired smartphone keyboard interactions may be useful to monitor progression in multiple sclerosis (MS). We aimed to study the correlation between tapping speed (TS), measured as keys/s, and baseline disability scales in patients with MS. Methods: Single-center prospective study in patients with MS. We passively assessed TS during first week, measured by an "in house" smartphone application. Reliability was assessed by intraclass correlation coefficient (ICC). Correlations between median and maximum keys/s of first week of assessment and baseline disability measures were explored. Results: One-hundred three patients were included: 62.1 % women, with a median (IQR) age of 47 (40.4-54.8) years-old and an EDSS score of 3.0 (2.0-4.0). Distribution by MS subtypes was: 77.7 % relapsing-remitting MS (RRMS), 17.5 % secondary-progressive MS (SPMS) and 4.9 % primary-progressive MS (PPMS). ICC during first week was 0.714 (p < 0.00001). Both median and maximum keys/s showed a negative correlation with Expanded Disability Status Score, 9-hole peg test and timed 25-foot walk and a positive correlation with Processing Speed Test CogEval® raw and Z-score. Median and maximum keys/s were lower in patients diagnosed with SPMS than in RRMS. Both measures of tapping speed were associated with MS phenotype independently of age. Conclusion: TS measured through our application is reliable and correlates with baseline disability scales.
Language	English
Publishing date	2024-03-30
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2024.105595
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Article ; Online: Soluble CD27 is an intrathecal biomarker of T-cell-mediated lesion activity in multiple sclerosis.

Cencioni, Maria T / Magliozzi, Roberta / Palmisano, Ilaria / Suwan, Keittisak / Mensi, Antonella / Fuentes-Font, Laura / Villar, Luisa M / Fernández-Velasco, José I / Migallón, Noelia Villarrubia / Costa-Frossard, Lucienne / Monreal, Enric / Ali, Rehiana / Romozzi, Marina / Mazarakis, Nicholas / Reynolds, Richard / Nicholas, Richard / Muraro, Paolo A

Journal of neuroinflammation

2024 Volume 21, Issue 1, Page(s) 91

Abstract: Objective: Soluble CD27 is a promising cerebrospinal fluid inflammatory biomarker in multiple sclerosis. In this study, we investigate relevant immune and neuro-pathological features of soluble CD27 in multiple sclerosis.: Methods: Protein levels of ... ...

Abstract	Objective: Soluble CD27 is a promising cerebrospinal fluid inflammatory biomarker in multiple sclerosis. In this study, we investigate relevant immune and neuro-pathological features of soluble CD27 in multiple sclerosis. Methods: Protein levels of soluble CD27 were correlated to inflammatory cell subpopulations and inflammatory cytokines and chemokines detected in cerebrospinal fluid of 137 patients with multiple sclerosis and 47 patients with inflammatory and non-inflammatory neurological disease from three independent cohorts. Production of soluble CD27 was investigated in cell cultures of activated T and B cells and CD27-knockout T cells. In a study including matched cerebrospinal fluid and post-mortem brain tissues of patients with multiple sclerosis and control cases, levels of soluble CD27 were correlated with perivascular and meningeal infiltrates and with neuropathological features. Results: We demonstrate that soluble CD27 favours the differentiation of interferon-γ-producing T cells and is released through a secretory mechanism activated by TCR engagement and regulated by neutral sphingomyelinase. We also show that the levels of soluble CD27 correlate with the representation of inflammatory T cell subsets in the CSF of patients with relapsing-remitting multiple sclerosis and with the magnitude of perivascular and meningeal CD27 + CD4 + and CD8 + T cell infiltrates in post-mortem central nervous system tissue, defining a subgroup of patients with extensive active inflammatory lesions. Interpretation: Our results demonstrate that soluble CD27 is a biomarker of disease activity, potentially informative for personalized treatment and monitoring of treatment outcomes.
MeSH term(s)	Humans ; Multiple Sclerosis ; Multiple Sclerosis, Relapsing-Remitting ; CD8-Positive T-Lymphocytes ; Central Nervous System ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2024-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	2156455-3
ISSN	1742-2094 ; 1742-2094
ISSN (online)	1742-2094
ISSN	1742-2094
DOI	10.1186/s12974-024-03077-9
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Article ; Online: Clusterin deficiency is associated with a lack of response to teriflunomide in multiple sclerosis.

Malhotra, Sunny / Fissolo, Nicolas / Rodríguez-Rivera, Carmen / Monreal, Enric / Montpeyo, Marta / Urcelay, Elena / Triviño, Juan Carlos / Pérez-García, María José / Segura, Miguel F / Pappolla, Agustín / Río, Jordi / Vilaseca, Andreu / Fernández Velasco, José Ignacio / Miguez, Andrés / Goicoechea, Carlos / Martinez-Vicente, Marta / Villar, Luisa M / Montalban, Xavier / Comabella, Manuel

Clinical and translational medicine

2024 Volume 14, Issue 4, Page(s) e1654

MeSH term(s)	Humans ; Multiple Sclerosis/drug therapy ; Clusterin ; Crotonates/therapeutic use ; Toluidines/therapeutic use ; Hydroxybutyrates ; Nitriles
Chemical Substances	teriflunomide (1C058IKG3B) ; Clusterin ; Crotonates ; Toluidines ; Hydroxybutyrates ; Nitriles
Language	English
Publishing date	2024-04-09
Publishing country	United States
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2697013-2
ISSN	2001-1326 ; 2001-1326
ISSN (online)	2001-1326
ISSN	2001-1326
DOI	10.1002/ctm2.1654
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Article ; Online: In reply to «HIV screening and its possible involvement in patients with stroke».

Monreal, Enric / Martínez-Sanz, Javier / Quereda Rodríguez-Navarro, Carmen / Corral, Íñigo

Enfermedades infecciosas y microbiologia clinica (English ed.)

2020 Volume 38, Issue 7, Page(s) 351–352

Title translation	En respuesta a «Cribado para la detección de VIH y su posible implicación en los pacientes con ictus».
MeSH term(s)	HIV Infections/complications ; HIV Infections/drug therapy ; Humans ; Mass Screening ; Serologic Tests ; Spain ; Stroke
Language	Spanish
Publishing date	2020-05-26
Document type	Letter ; Comment
ISSN	2529-993X
ISSN (online)	2529-993X
DOI	10.1016/j.eimc.2020.03.010
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Article ; Online: The effect of timing of high-efficacy therapy on processing speed performance in multiple sclerosis.

Labiano-Fontcuberta, Andrés / Costa-Frossard, Lucienne / Sainz de la Maza, Susana / Rodríguez-Jorge, Fernando / Chico-García, Juan Luis / Monreal, Enric

Multiple sclerosis and related disorders

2022 Volume 64, Page(s) 103959

Abstract: Background: The potential influence of the timing of high-efficacy disease-modifying therapies (heDMTs) on processing speed (PS) performance is critically lacking in current literature.: Objective: To assess the extent to which early commencement of ... ...

Abstract	Background: The potential influence of the timing of high-efficacy disease-modifying therapies (heDMTs) on processing speed (PS) performance is critically lacking in current literature. Objective: To assess the extent to which early commencement of heDMTs would be associated with a better PS evolution as compared to moderate efficacy disease-modifying therapies (meDMTs) and delayed commencement of heDMTs. Methods: In this ongoing prospective longitudinal study, the 695 MS patients that have received a PS evaluation at 12-month of follow-up measured by the iPad®-based Processing Speed Test (PST) were retained for the analysis. All patients who had ever been prescribed a high efficacy disease-modifying therapy (heDMT) were classified in tertiles according to the proportion of their disease duration that had been on heDMTs. Based on these tertiles and the time to the first heDMT from the disease onset, patients were divided into the early heDMT group and the delayed heDMT group. Between-group differences in mean PST standardized (Z-score) change from baseline were analyzed using a linear mixed model. Results: In the multivariable model, each year of delay in starting a heDMT was associated with increased odds of cognitive worsening at 12-month (OR = 1.0324, 95% CI = 1.014-1.062, p<0.05). MeDMT-treated patients were at a significantly higher risk for cognitive worsening than early heDMT patients (OR= 2.57, 95%CI = 1.02-6.17). Linear mixed model-based adjusted mean change in PST Z-score from baseline was significantly better in those patients with the longest proportion of their disease duration treated with heDMT (highest tertile) compared to the lowest tertile (difference 0.37 [95%CI 0.02-0.92;p=0.036) and medium tertile (difference 0.39 [95%CI 0.06-0.31;p=0.037). Conclusion: Early he-DMT-treated patients are at significantly lower risk for cognitive worsening. Early administration of heDMTs is associated with greater cognitive functioning improvements than delayed commencement or meDMTs.
MeSH term(s)	Cognition ; Humans ; Longitudinal Studies ; Multiple Sclerosis/complications ; Multiple Sclerosis, Relapsing-Remitting/complications ; Prospective Studies
Language	English
Publishing date	2022-06-10
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2022.103959
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Article ; Online: Predictive models of multiple sclerosis-related cognitive performance using routine clinical practice predictors.

Labiano-Fontcuberta, Andrés / Costa-Frossard, Lucienne / Sainz de la Maza, Susana / Rodríguez-Jorge, Fernando / Chico-García, Juan Luis / González, Pablo Nieto / Monreal, Enric

Multiple sclerosis and related disorders

2023 Volume 76, Page(s) 104849

Abstract: Background: The application of machine learning (ML) to predict cognitive evolution is exceptionally scarce. Computer-based self-administered cognitive tests provide the opportunity to set up large longitudinal datasets to aid in developing ML ... ...

Abstract	Background: The application of machine learning (ML) to predict cognitive evolution is exceptionally scarce. Computer-based self-administered cognitive tests provide the opportunity to set up large longitudinal datasets to aid in developing ML prediction models of risk for Multiple Sclerosis-related cognitive decline. Objective: to analyze to what extent clinically feasible models can be built with standard clinical practice features and subsequently used for reliable prediction of cognitive evolution. Methods: This prospective longitudinal study includes 1184 people with MS who received a Processing Speed (PS) evaluation at 12 months of follow-up measured by the iPad®-based Processing Speed Test (PST). Six of the most potent classification models built with routine clinical practice features were trained and tested to predict the 12-month patient class label (PST worsening (PSTw) versus PST stable). A rigorous scheme of all the preprocessing steps run to obtain reliable generalization performance is detailed. Results: Based on a 12-month reduction of 10% of the PST raw score, 187/1184 (15.8%) people with MS were classified as PSTw. The trees-based models (random forest and the eXtreme Gradient Boosting) achieved the best performance, with an area under the receiver operating characteristic curve (AUC) of 0.90 and 0.89, respectively. The timing of high-efficacy disease-modifying therapies (heDMTs) was identified as one of the top importance predictors in all the models evaluated. Conclusion: Using trees-based machine learning models to predict individual future information processing speed deterioration in MS could become a reality in clinical practice.
MeSH term(s)	Humans ; Multiple Sclerosis/complications ; Multiple Sclerosis/diagnosis ; Prospective Studies ; Longitudinal Studies ; Cognition ; Cognitive Dysfunction/diagnosis ; Cognitive Dysfunction/etiology
Language	English
Publishing date	2023-06-21
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2645330-7
ISSN	2211-0356 ; 2211-0348
ISSN (online)	2211-0356
ISSN	2211-0348
DOI	10.1016/j.msard.2023.104849
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Article: Emerging biomarkers for improving pregnancy planning in multiple sclerosis.

Cuello, Juan Pablo / Meldaña Rivera, Ariana / Monreal, Enric / Gómez Lozano, Ana / García Cano, Ana Maria / García Domínguez, Jose Manuel / Fernández Velasco, José Ignacio / Costa-Frossard França, Lucienne / Goicochea, Haydee / Higueras, Yolanda / De León-Luis, Juan Antonio / Sainz De La Maza, Susana / Villarrubia, Noelia / Arribas Gómez, Ignacio / Ruiz Perez, Irene / Martinez Ginés, Maria Luisa / Villar, Luisa María

Frontiers in neurology

2024 Volume 15, Page(s) 1292296

Abstract: Background: Patient disability, relapse rate, and age are used for family planning in multiple sclerosis (MS). However, the need for more accurate biomarkers is widely recognized. We aimed to explore the influence of age on neurofilament light chain ( ... ...

Abstract	Background: Patient disability, relapse rate, and age are used for family planning in multiple sclerosis (MS). However, the need for more accurate biomarkers is widely recognized. We aimed to explore the influence of age on neurofilament light chain (sNfL), which reflects acute inflammation; glial fibrillary acidic protein (GFAP), associated with disability progression independent of relapses; and anti-Müllerian hormone (AMH), reflecting ovarian reserve, to provide a tailored family planning strategy. Methods: This case-control study included 95 MS patients and 61 healthy control women (HCW). sNfL and GFAP levels were measured using a sensitive single-molecule array assay. AMH levels were measured by the automated Elecsys Results: We observed no significant differences in AMH values between MS patients and the control group within any of the age-matched categories. Age exhibited a negative correlation with AMH values in both groups, as expected. Nevertheless, our findings suggest a slight tendency toward reduced ovarian reserve in MS patients (rho MS patients = -0.67, Conclusion: We found no significant differences in AMH, sNfL or GFAP values between MS patients and the control group within any of the age-matched categories. The assessment of AMH, sNFL and GFAP levels at MS onset facilitates personalized therapeutic and family planning strategies for childbearing-age women.
Language	English
Publishing date	2024-02-15
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2564214-5
ISSN	1664-2295
ISSN	1664-2295
DOI	10.3389/fneur.2024.1292296
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Article: Blood CD8+ Naïve T-Cells Identify MS Patients with High Probability of Optimal Cellular Response to SARS-CoV-2 Vaccine.

Rodero-Romero, Alexander / Sainz de la Maza, Susana / Fernández-Velasco, José Ignacio / Monreal, Enric / Walo-Delgado, Paulette Esperanza / Chico-García, Juan Luis / Villarrubia, Noelia / Rodríguez-Jorge, Fernando / Rodríguez-Ramos, Rafael / Masjuan, Jaime / Costa-Frossard, Lucienne / Villar, Luisa María

Vaccines

2023 Volume 11, Issue 9

Abstract: This single-center study included 68 multiple sclerosis (MS) patients who received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from one of several approved vaccine preparations in Spain. Blood samples were collected one ... ...

Abstract	This single-center study included 68 multiple sclerosis (MS) patients who received the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination from one of several approved vaccine preparations in Spain. Blood samples were collected one to three months after the second dose of the vaccine had been administered. Cellular immune responses to the vaccine were assessed using QuantiFERON analysis, and peripheral blood mononuclear cell subsets were assayed using flow cytometry. Response associated with higher percentages of total lymphocytes, naïve CD4+ T-cells (
Language	English
Publishing date	2023-08-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11091399
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Article: Short- and Long-Term Humoral and Cellular Immune Responses to SARS-CoV-2 Vaccination in Patients with Multiple Sclerosis Treated with Disease-Modifying Therapies.

Sainz de la Maza, Susana / Walo-Delgado, Paulette Esperanza / Rodríguez-Domínguez, Mario / Monreal, Enric / Rodero-Romero, Alexander / Chico-García, Juan Luis / Pariente, Roberto / Rodríguez-Jorge, Fernando / Ballester-González, Rubén / Villarrubia, Noelia / Romero-Hernández, Beatriz / Masjuan, Jaime / Costa-Frossard, Lucienne / Villar, Luisa María

Vaccines

2023 Volume 11, Issue 4

Abstract: Background: This study aimed to evaluate short- and long-term humoral and T-cell-specific immune responses to SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs).: Methods: Single- ... ...

Abstract	Background: This study aimed to evaluate short- and long-term humoral and T-cell-specific immune responses to SARS-CoV-2 vaccines in patients with multiple sclerosis (MS) treated with different disease-modifying therapies (DMTs). Methods: Single-center observational longitudinal study including 102 patients with MS who consecutively received vaccination against SARS-CoV-2. Serum samples were collected at baseline and after receiving the second dose of the vaccine. Specific Th1 responses following in vitro stimulation with spike and nucleocapsid peptides were analyzed by quantifying levels of IFN-γ. Serum IgG-type antibodies against the spike region of SARS-CoV-2 were studied by chemiluminescent microparticle immunoassay. Results: Patients undergoing fingolimod and anti-CD20 therapies had a markedly lower humoral response than those treated with other DMTs and untreated patients. Robust antigen-specific T-cell responses were detected in all patients except those treated with fingolimod, who had lower IFN-γ levels than those treated with other DMTs (25.8 pg/mL vs. 868.7 pg/mL, Conclusions: SARS-CoV-2 vaccines induce robust and long-lasting humoral and cell-mediated specific immune responses in most patients with MS.
Language	English
Publishing date	2023-04-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2703319-3
ISSN	2076-393X
ISSN	2076-393X
DOI	10.3390/vaccines11040786
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