R Arroyo

Hospital Clínico San Carlos, Madrid, Madrid, Spain

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Publications (64)278.52 Total impact

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    ABSTRACT: The presence of oligoclonal IgM bands (OCMB) in cerebrospinal fluid (CSF) is an unfavourable prognostic marker in multiple sclerosis. There is no commercial test to investigate OCMB status. However, a sensitive and specific isoelectrofocusing (IEF) and western blot method was described. We aimed to study the inter-centre reproducibility of this technique, a necessary condition for a reliable test to be incorporated into clinical practice.
    Clinica Chimica Acta. 08/2014; 438.
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    ABSTRACT: Background and purposeDifferent data show an association between human herpesvirus 6 (HHV-6) and multiple sclerosis (MS). Intrathecal anti-HHV-6 immunoglobulin G (IgG) was detected in MS patients, but the antigen recognized by cerebrospinal fluid (CSF) IgG has not been characterized yet. Our objective was to identify the HHV-6 antigens recognized by IgG present in the CSF of patients with MS.Methods Cerebrospinal fluid IgG of 15 MS patients and eight patients with other neurological diseases was purified on protein G Sepharose columns. Purified IgG from every patient was linked to a CNBr-activated Sepharose 4B column. Fifty micrograms of viral extract was applied to each column. Bound proteins were eluted and analysed by SDS-PAGE and silver staining. The viral protein was characterized by mass spectrometry.ResultsA protein of 150 kD was eluted from CSF IgG columns of three of eight patients with primary progressive MS and one of seven with relapsing−remitting MS. After digestion and mass spectrometry analysis 10 peptides were found with 100% homology with the major capsid protein of the HHV-6A.DiscussionThese findings confirm the presence of anti-HHV-6 IgG in CSF of MS patients, particularly in progressive forms, and identify major capsid protein as the major antigen recognized by CSF IgG from MS patients.
    European Journal of Neurology 04/2014; · 4.16 Impact Factor
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    ABSTRACT: The use of culture-dependent and -independent techniques to study the human milk microbiota and microbiome has revealed a complex ecosystem with a much greater diversity than previously anticipated. The potential role of the milk microbiome appears to have implications not only for short- and long-term infant health but also for mammary health. In fact, mammary disbiosis, which may be triggered by a variety of host, microbial and medical factors, often leads to acute, subacute or subclinical mastitis, a condition that represents the first medical cause for undesired weaning. Multiresistance to antibiotics, together with formation of biofilms and mechanisms for evasion of the host immune response, is a common feature among the bacterial agents involved. This explains why this condition uses to be elusive to antibiotic therapy and why the development of new strategies for mastitis management based on probiotics is particularly appealing. In fact, selected lactobacilli strains isolated from breast milk have already shown a high efficacy for treatment.
    Beneficial Microbes 01/2014; · 1.47 Impact Factor
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    ABSTRACT: A recent genome-wide association study reported five loci for which there was strong, but sub-genome-wide significant evidence for association with multiple sclerosis risk. The aim of this study was to evaluate the role of these potential risk loci in a large and independent data set of ∼20 000 subjects. We tested five single nucleotide polymorphisms rs228614 (MANBA), rs630923 (CXCR5), rs2744148 (SOX8), rs180515 (RPS6KB1), and rs6062314 (ZBTB46) for association with multiple sclerosis risk in a total of 8499 cases with multiple sclerosis, 8765 unrelated control subjects and 958 trios of European descent. In addition, we assessed the overall evidence for association by combining these newly generated data with the results from the original genome-wide association study by meta-analysis. All five tested single nucleotide polymorphisms showed consistent and statistically significant evidence for association with multiple sclerosis in our validation data sets (rs228614: odds ratio = 0.91, P = 2.4 × 10(-6); rs630923: odds ratio = 0.89, P = 1.2 × 10(-4); rs2744148: odds ratio = 1.14, P = 1.8 × 10(-6); rs180515: odds ratio = 1.12, P = 5.2 × 10(-7); rs6062314: odds ratio = 0.90, P = 4.3 × 10(-3)). Combining our data with results from the previous genome-wide association study by meta-analysis, the evidence for association was strengthened further, surpassing the threshold for genome-wide significance (P < 5 × 10(-8)) in each case. Our study provides compelling evidence that these five loci are genuine multiple sclerosis susceptibility loci. These results may eventually lead to a better understanding of the underlying disease pathophysiology.
    Brain 06/2013; 136(6):1778-82. · 10.23 Impact Factor
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    ABSTRACT: BACKGROUND AND PURPOSE: Toll-like receptor-9 (TLR9) is a potent inducer of innate immune system triggered by infection with viruses, some of them previously related to multiple sclerosis (MS). The aim of this study was to analyze the possible association of two TLR9 single nucleotide polymorphisms (SNPs; rs352162 and rs187084) with susceptibility to MS. METHODS: Two independent cohorts of MS patients and controls were included: 574 clinically definite relapsing-remitting MS patients (367 females) and 807 healthy controls (418 females) for the first cohort; and 366 relapsing-remitting MS patients (238 females) and 224 healthy controls (160 females) for the second cohort. Genotyping was performed by TaqMan assays. RESULTS: The AT haplotype was found to be significantly higher in women than in men (P = 0.013 and P = 0.044). CONCLUSIONS: Here two possible genetic markers are proposed that could be also associated with the differences observed in the clinical course of MS in both genders. Further studies with larger cohorts should be performed to confirm these results.
    European Journal of Neurology 06/2013; · 4.16 Impact Factor
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    ABSTRACT: OBJECTIVE: In Assessment of OraL Laquinimod in PrEventing ProGRession in Multiple SclerOsis (ALLEGRO), a phase III study in relapsing-remitting multiple sclerosis (RRMS), oral laquinimod slowed disability and brain atrophy progression, suggesting laquinimod may reduce tissue damage in MS. MRI techniques sensitive to the most destructive aspects of the disease were used to further investigate laquinimod's potential effects on inflammation and neurodegeneration. METHODS: 1106 RRMS patients were randomised 1:1 to receive once-daily oral laquinimod (0.6 mg) or placebo for 24 months. White matter (WM), grey matter (GM) and thalamic fractions were derived at months 0, 12 and 24. Also assessed were evolution of gadolinium-enhancing and/or new T2 lesions into permanent black holes (PBH); magnetisation transfer ratio (MTR) of normal-appearing brain tissue (NABT), WM, GM and T2 lesions; and N-acetylaspartate/creatine (NAA/Cr) levels in WM. RESULTS: Compared with placebo, laquinimod-treated patients showed lower rates of WM at months 12 and 24 (p=0.004 and p=0.035) and GM (p=0.004) atrophy at month 12 and a trend for less GM atrophy at month 24 (p=0.078). Laquinimod also slowed thalamic atrophy at month 12 (p=0.005) and month 24 (p=0.003) and reduced the number of PBH at 12 and 24 months evolving from active lesions (all p<0.05). By month 24, MTR decreased significantly in NABT (p=0.015), WM (p=0.011) and GM (p=0.034) in placebo-treated patients, but not in laquinimod-treated patients. WM NAA/Cr tended to increase with laquinimod and decrease with placebo at 24 months (p=0.179). CONCLUSIONS: Oral laquinimod may reduce (at least in the initial phase of treatment) some of the more destructive pathological processes in RRMS patients. TRIAL REGISTRATION: The ALLEGRO trial identifier number with clinicaltrials.gov is NCT00509145. KEYWORDS: MRI, Multiple Sclerosis
    Journal of neurology, neurosurgery, and psychiatry 01/2013; · 4.87 Impact Factor
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    ABSTRACT: Introduction Natalizumab treatment has been shown to be very efficacious in clinical trials and very effective in clinical practice in patients with relapsing-remitting multiple sclerosis, by reducing relapses, slowing disease progression, and improving magnetic resonance imaging patterns. However, the drug has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The first consensus statement on natalizumab use, published in 2011, has been updated to include new data on diagnostic procedures, monitoring for patients undergoing treatment, PML management, and other topics of interest including the management of patients discontinuing natalizumab. Material and methods This updated version followed the method used in the first consensus. A group of Spanish experts in multiple sclerosis (the authors of the present document) reviewed all currently available literature on natalizumab and identified the relevant topics would need updating based on their clinical experience. The initial draft passed through review cycles until the final version was completed. Results and conclusions Studies in clinical practice have demonstrated that changing to natalizumab is more effective than switching between immunomodulators. They favour early treatment with natalizumab rather than using natalizumab in a later stage as a rescue therapy. Although the drug is very effective, its potential adverse effects need to be considered, with particular attention to the patient's likelihood of developing PML. The neurologist should carefully explain the risks and benefits of the treatment, comparing them to the risks of multiple sclerosis in terms the patient can understand. Before treatment is started, laboratory tests and magnetic resonance images should be available to permit proper follow-up. The risk of PML should be stratified as high, medium, or low according to presence or absence of anti-JC virus antibodies, history of immunosuppressive therapy, and treatment duration. Although the presence of anti-JC virus antibodies is a significant finding, it should not be considered an absolute contraindication for natalizumab. This update provides general recommendations, but neurologists must use their clinical expertise to provide personalised follow-up for each patient.
    Neurología. 01/2013;
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    ABSTRACT: Deterioration of diverse coastal ecosystems of the world, including Mexico, is partly a result of the lack of tools for economic valuation of the elements of these environments, which can contribute to their conservation and management. Additionally, where accidental or deliberate human activities impact these ecosystems, this information is necessary to allocate responsibilities and to determine costs for rehabilitation of the altered systems. Regarding this, a multidisciplinary group of experts on coastal zone, developed a methodology to estimate the economic value (VE) for different coastal environments, referred as value/ ha/year, which can be extrapolated to Total Economic Value (VET), when the extent of the ecosystem and its components is known. Initially, a hypothetical exercise was run assigning economic values based on the specialists’ experience. The VET for each of the four ecosystems of the Mexican Pacific included in this study, was estimated based on a compilation of values (U.S. dollars) estimated at international extent. Regarding the heterogeneity of the coastal ecosystems and their environmental services, coastal features for the economic evaluation (VET) analysis were selected by the experts following the criteria by Millennium Ecosystem Assessment.
    Investigación Ambiental Ciencia y política pública. 01/2013; 5:7-32.
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    ABSTRACT: Lactic acid bacteria (LAB) isolated from soy milk were used to produce a multifunctional fermented food. Seven isolates were screened for their ability to produce peptides and free isoflavones in soy milk. The antihypertensive, antioxidant, and anti-inflammatory properties of the resulting fermented soy milks were evaluated in vitro using biochemical assays. Isolates 1-5 were found to be producers of fermented soy milk with angiotensin I converting enzyme inhibitory activity (ACEI). Isolate 3 was found to be a producer of free isoflavones that increased the antioxidant and anti-inflammatory potential of fermented soy milk. LAB isolates 2-5 were submitted to genetic profiling and a characterization scheme. These isolates were identified as Enterococcus faecium , and none of them contained virulence determinants or resistance to antibiotics. In conclusion, this study shows that the application of E. faecium isolate 3 for multifunctional food production from soy milk could be a promising strategy in the prevention therapy against cardiovascular disease.
    Journal of Agricultural and Food Chemistry 09/2012; 60(41):10235-44. · 3.11 Impact Factor
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    ABSTRACT: Bifidobacterium breve is an actinobacterium frequently isolated from colonic microbiota of breastfeeding babies. Here, we report the complete and annotated genome sequence of a B. breve strain isolated from human milk, B. breve CECT 7263. The genome sequence will provide new insights into the biology of this potential probiotic organism and will allow the characterization of genes related to beneficial properties.
    Journal of bacteriology 07/2012; 194(14):3762-3. · 3.94 Impact Factor
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    ABSTRACT: Recently, we reported an association between a SNP in IL28RA and MS. Here, we performed a fine-mapping of the IL28RA locus by genotyping 10 haplotype-tagging SNPs in a Basque-Spanish population. In addition, based on shared genetic risk loci between autoimmune diseases, a psoriasis-associated SNP located at this locus, rs4649203, was genotyped in four independent populations, comprising a total of 2582 cases and 2614 controls. We did not find any consistent association between IL28RA and MS in these populations, suggesting that, although it may play a role in other autoimmune diseases, this gene is unlikely of general relevance to MS pathogenesis.
    Journal of neuroimmunology 03/2012; 245(1-2):98-101. · 2.84 Impact Factor
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    ABSTRACT: Natalizumab has been shown to be effective in pivotal clinical trials in multiple sclerosis; however, the patients in whom treatment is indicated in clinical practice have a different clinical profile from those included in the clinical trials. The aim of this study is therefore to collect data on natalizumab use in everyday clinical practice in Spain. The 86 participating centers throughout Spain submitted data on disease characteristics at baseline and after treatment. Valid data were available for 1,364 patients (69.3% women, 86.9% with relapsing-remitting disease). Ninety-three percent had received prior therapy for multiple sclerosis. For the 825 patients on treatment for at least a year, the annualized relapse rate (ARR) decreased from median 2.0 [mean 2.01, 95% confidence interval (CI) 1.92-2.11] in the year prior to natalizumab to 0.0 (mean 0.25, 95% CI 0.21-0.29) at 1 year (p < 0.001). The Expanded Disability Status Scale (EDSS) score decreased from median 3.5 at baseline (mean 3.71, 95% CI 3.60-3.82) to 3.0 (mean 3.37, 95% CI 3.25-3.49) (p < 0.0001). The discontinuation rate was 14%. One patient discontinued natalizumab due to progressive multifocal leukoencephalopathy (PML) and another due to probable PML (subsequently confirmed). Although our patients had more severe disease than those in the pivotal study, a similar reduction in ARR was observed. This finding is in line with previous observational studies. The effect was independent of baseline EDSS.
    Journal of Neurology 01/2012; · 3.58 Impact Factor
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    ABSTRACT: BACKGROUND: Two proof-of-concept clinical trials have provided evidence that laquinimod reduces disease activity in patients with relapsing-remitting multiple sclerosis. METHODS: We conducted a randomized, double-blind, phase 3 study at 139 sites in 24 countries. A total of 1106 patients with relapsing-remitting multiple sclerosis were randomly assigned in a 1:1 ratio to receive oral laquinimod at a dose of 0.6 mg once daily or placebo for 24 months. The primary end point was the annualized relapse rate during the 24-month period. Secondary end points included confirmed disability progression (defined as an increase in the score on the Expanded Disability Status Scale that was sustained for at least 3 months) and the cumulative number of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted magnetic resonance imaging. RESULTS: Treatment with laquinimod as compared with placebo was associated with a modest reduction in the mean (±SE) annualized relapse rate (0.30±0.02 vs. 0.39±0.03, P=0.002) and with a reduction in the risk of confirmed disability progression (11.1% vs. 15.7%; hazard ratio, 0.64; 95% confidence interval, 0.45 to 0.91; P=0.01). The mean cumulative numbers of gadolinium-enhancing lesions and new or enlarging lesions on T(2)-weighted images were lower for patients receiving laquinimod than for those receiving placebo (1.33±0.14 vs. 2.12±0.22 and 5.03±0.08 vs. 7.14±0.07, respectively; P<0.001 for both comparisons). Transient elevations in alanine aminotransferase levels to greater than three times the upper limit of the normal range were observed in 24 patients receiving laquinimod (5%) and 8 receiving placebo (2%). CONCLUSIONS: In this phase 3 study, oral laquinimod administered once daily slowed the progression of disability and reduced the rate of relapse in patients with relapsing-remitting multiple sclerosis. (Funded by Teva Pharmaceutical Industries; ClinicalTrials.gov number, NCT00509145.). Comment in Oral laquinimod for multiple sclerosis. [N Engl J Med. 2012] New and old: notable drug developments for clinical practice. [J Neurol. 2012]
    New England Journal of Medicine 01/2012; 366(11):1000-1009. · 54.42 Impact Factor
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    ABSTRACT: Chitinase 3-like 1 (CHI3L1) is upregulated in a wide variety of inflammatory conditions. Recent studies have pointed to a role of CHI3L1 in multiple sclerosis (MS) pathogenesis. The objective of this study was to investigate the role of plasma CHI3L1 in MS clinical course and disease activity and to evaluate the effect of interferon-beta (IFNβ) treatment on protein levels. Plasma CHI3L1 levels were determined by ELISA in 57 healthy controls (HC), 220 untreated MS patients [66 primary progressive MS patients (PPMS), 30 secondary progressive MS patients (SPMS), and 124 relapsing-remitting MS patients (RRMS), 94 during clinical remission and 30 during relapse], and 32 MS patients receiving IFNβ treatment. A polymorphism of the CHI3L1 gene, rs4950928, was genotyped in 3274 MS patients and 3483 HC. Plasma CHI3L1 levels were significantly increased in patients with progressive forms of MS compared with RRMS patients and HC. CHI3L1 levels were similar between RRMS patients in relapse and remission. A trend towards decreased CHI3L1 levels was observed in IFNβ-treated patients. Allele C of rs4950928 was significantly associated with PPMS patients and with higher plasma CHI3L1 levels. These findings point to a role of CHI3L1 in patients with progressive forms of MS, particularly in those with PPMS.
    Multiple Sclerosis 12/2011; 18(7):983-90. · 4.47 Impact Factor
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    ABSTRACT: Multiple sclerosis (MS) shares some risk genes with other disorders hallmarked by an autoimmune pathogenesis, most notably IL2RA and CLEC16A. We analyzed 10 single-nucleotide polymorphisms (SNPs) in nine risk genes, which recently emerged from a series of non-MS genome-wide association studies (GWAS), in a Spanish cohort comprising 2895 MS patients and 2942 controls. We identified two SNPs associated with MS. The first SNP, rs6859219, located in ANKRD55 (Chr5), was recently discovered in a meta-analysis of GWAS on rheumatoid arthritis (RA), and emerged from this study with genome-wide significance (odds ratio (OR) = 1.35; P = 2.3 × 10(-9)). The second SNP, rs12785878, is located near DHCR7 (Chr11), a genetic determinant of vitamin D insufficiency, and showed a size effect in MS similar to that recently observed in Type 1 diabetes (T1D; OR = 1.10; P = 0.009). ANKRD55 is a gene of unknown function, and is flanked proximally by the IL6ST-IL31RA gene cluster. However, rs6859219 did not show correlation with a series of haplotype-tagging SNPs covering IL6ST-IL31RA, analyzed in a subset of our dataset (D'< 0.31; r(2)< 0.011). Our results expand the number of risk genes shared between MS, RA and T1D.
    Genes and immunity 12/2011; 13(3):253-7. · 4.22 Impact Factor
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    ABSTRACT: Natalizumab is very effective at reducing relapses and delaying disease progression in patients with relapsing-remitting multiple sclerosis (RRMS). However, treatment has also been associated with a risk of progressive multifocal leukoencephalopathy (PML). The aim of this article is to provide a consensus view on the assessment and stratification of these risks, and to improve the management of natalizumab-treated patients. At an initial meeting of experts on multiple sclerosis (the authors of this consensus), the relevant topics of the consensus were determined and assigned for further elaboration. Topics included how to establish benefit and risk in general, stratification for risk of PML, informing patients of benefits/risks, and how to monitor patients during treatment and after discontinuing treatment. During the drafting phase, all available information published or presented at international meetings was reviewed. After a series of review sessions and meetings, the final draft was produced. Although natalizumab is a very effective drug, its use needs to be considered carefully in view of possible adverse effects and the risk of PML in particular. The neurologist should carefully explain the risks and benefits of treatment in terms the patient can best understand. Before starting treatment, baseline laboratory tests and magnetic resonance imaging (MRI) should be available for future comparisons in the event of suspected PML. The risk of PML should be stratified into high, medium and low risk groups according to presence or absence of anti-JC virus antibodies, prior immunosuppressive therapy, and treatment duration. The follow-up, and frequency of MRI scans in particular, should depend on the risk group to which patient belongs. As our understanding of the risk factors for PML develops, it should be possible to offer patients increasingly individualised therapy. This is a consensus that establishes general recommendations, but neurologists must use their clinical expertise to monitor patients individually.
    Neurologia 11/2011; 27(7):432-41.
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    ABSTRACT: Cytokine and cytokine receptor genes, including IL2RA, IL7R and IL12A, are known risk factors for multiple sclerosis (MS). Excitotoxic oligodendroglial death mediated by glutamate receptors contributes to demyelinating reactions. In the present study, we screened 368 single-nucleotide polymorphisms (SNPs) in 55 genes or gene clusters coding for cytokines, cytokine receptors, suppressors of cytokine signaling (SOCS), complement factors and glutamate receptors for association with MS in a Spanish-Basque resident population. Top-scoring SNPs were found within or nearby the genes coding for SOCS-1 (P=0.0005), interleukin-28 receptor, alpha chain (P=0.0008), oncostatin M receptor (P=0.002) and interleukin-22 receptor, alpha 2 (IL22RA2; P=0.003). The SOCS1 rs243324 variant was validated as risk factor for MS in a separate cohort of 3919 MS patients and 4003 controls (combined Cochran-Mantel-Haenszel P=0.00006; odds ratio (OR)=1.13; 95% confidence interval (CI)=1.07-1.20). In addition, the T allele of rs243324 was consistently increased in relapsing-remitting/secondary progressive versus primary-progressive MS patients, in each of the six data sets used in this study (P(CMH)=0.0096; OR=1.24; 95% CI 1.05-1.46). The association with SOCS1 appears independent from the chr16MS risk locus CLEC16A.
    Genes and immunity 06/2011; 13(1):21-8. · 4.22 Impact Factor
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    ABSTRACT: An early and accurate diagnosis of multiple sclerosis (MS) is very important, since it allows early treatment initiation, which reduces the activity of the disease. Oligoclonal IgG band (OCGB) detection is a good ancillary tool for MS diagnosis. However, it was argued that its usefulness was limited by the high interlaboratory variability. In the last years, different techniques for OCGB detection have appeared. We performed a blinded aleatorized multicenter study in 19 Spanish hospitals to assess the accuracy and reproducibility of OCGB detection in this new scenario. We studied cerebrospinal fluid (CSF) and serum samples from 114 neurological patients. Every hospital contributed to the study with triplicated pairs of CSF and serum samples of six patients and analyzed 18 different samples. Global analysis rendered a sensitivity of 92.1%, a specificity of 95.1% and a Kappa value of 0.81. This shows that current techniques for OCGB detection have good accuracy and a high interlaboratory reproducibility and thus, represent a good tool for MS diagnosis. When we analyzed separately the different techniques used for OCGB detection, the highest concordance was observed in western blot with alkaline phosphatase detection (kappa=0.91). This indicates that high sensitivity techniques improve the reproducibility of this assay.
    Journal of immunological methods 06/2011; 371(1-2):170-3. · 2.35 Impact Factor
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    ABSTRACT:   Human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) have been repeatedly associated with multiple sclerosis (MS) pathogenesis. Also, it has been speculated that, besides its immunomodulatory properties, the efficacy of interferon beta (IFN-beta) in treating the disease may be related to its antiviral properties. The objectives of this study were to evaluate the in vivo antiviral effect of IFN-beta-1b over HHV-6 and EBV and to analyze whether such effect could be involved in its effectiveness in MS.   A total of 54 patients with MS were included in an observational, multicentric, 24-month study. HHV-6 and EBV were detected by qPCR in blood and serum samples. IFN-beta-1b effectiveness was evaluated by presence, number and severity of relapses, reduction in the relapse rate, disability progression, and response to the treatment.   Patients with HHV-6 in blood had a higher risk of severe relapses (P=0.01) and bad response (P=0.03). HHV-6 was detected more frequently during relapses than in remission in blood (P=0.024) and in serum (P=0.0002). Patients with HHV-6 in serum had more relapses (P=0.02), lesser reduction in the relapse rate (P=0.04), and a lower proportion of responders (P=0.02) than those without HHV-6 active replication. However, any association between EBV and clinical parameters could not be found.   We concluded that presence of HHV-6 in blood and serum during IFN-beta treatment could be a good marker of poor response.
    European Journal of Neurology 04/2011; 18(8):1027-35. · 4.16 Impact Factor
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    ABSTRACT: . We report a case of Balo's concentric sclerosis with peculiar MRI findings. Unlike previously published cases all concentric rings in our case showed marked enhancement, supporting the view of synchronous active demyelination in the lesion. Follow-up MRI disclosed a change of the lesions into a confluent pattern more resembling a typical large MS plaque. There were no oligoclonal bands or intrathecal Ig-G synthesis. The hypothesis concerning the pathophysiology of the lesions' typical and peculiar morphological appearance and its relationship to multiple sclerosis are briefly discussed.
    Neurologia 03/2011; 26(2):125-7.

Publication Stats

742 Citations
278.52 Total Impact Points

Institutions

  • 1996–2014
    • Hospital Clínico San Carlos
      • Servicio de Neurología
      Madrid, Madrid, Spain
    • Universidad de Extremadura
      Ara Pacis Augustalis, Extremadura, Spain
  • 2008–2012
    • Complutense University of Madrid
      • Departamento de Nutrición, Bromatología y Tecnología de los Alimentos
      Madrid, Madrid, Spain
  • 2011
    • Universidad del País Vasco / Euskal Herriko Unibertsitatea
      Leioa, Basque Country, Spain
    • Instituto de Investigación Sanitaria
      Madrid, Madrid, Spain
    • Hospital Universitario Ramón y Cajal
      Madrid, Madrid, Spain
  • 1994
    • University of San Carlos of Guatemala
      Guatemala la Nueva, Guatemala, Guatemala