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1. Impact of COVID-19 pandemic on frequency of clinical visits, performance of MRI studies, and therapeutic choices in a multiple sclerosis referral centre

Author: Alvaro Cobo-Calvo, Ana Zabalza, Jordi Río, Georgina Arrambide, Susana Otero-Romero, Paula Tagliani, Simón Cárdenas-Robledo, Mireia Castillo, Carmen Espejo, Marta Rodriguez, Pere Carbonell, Breogán Rodríguez, Luciana Midaglia, Ángela Vidal-Jordana, Carmen Tur, Ingrid Galan, Joaquín Castillo, Manuel Comabella, Carlos Nos, Cristina Auger, Mar Tintoré, Àlex Rovira, Xavier Montalban, and Jaume Sastre-Garriga
Subjects: Standards of care, Original Communication, Multiple Sclerosis, Neurology, SARS-CoV-2, COVID-19, Humans, Neurology (clinical), Magnetic Resonance Imaging, Pandemics, Referral and Consultation, Telemedicine, Retrospective Studies
Abstract: Introduction To evaluate the impact of the COVID-19 pandemic on (1) number of clinical visits, (2) magnetic resonance (MR) scans, and (3) treatment prescriptions in a multiple sclerosis (MS) referral centre. Methods Retrospective study covering January 2018 to May 2021. Results The monthly mean (standard deviation [SD]) of visits performed in 2020 (814[137.6]) was similar to 2018 (741[99.7]; p = 0.153), and 2019 (797[116.3]; p = 0.747). During the COVID-19 period (2020 year), 36.3% of the activity was performed through telemedicine. The number of MR scans performed dropped by 76.6% during the “first wave” (March 14 to June 21, 2020) compared to the mean monthly activity in 2020 (183.5[68.9]), with a recovery during the subsequent two months. The monthly mean of treatment prescriptions approved in 2020 (24.1[7.0]) was lower than in 2019 (30[7.0]; p = 0.049), but similar to 2018 (23.8[8.0]; p = 0.727). Natalizumab prescriptions increased in the “first wave” and onwards, whereas anti-CD20 prescriptions decreased during the COVID-19 period. Conclusion Maintenance of the number of clinical visits was likely due to telemedicine adoption. Although the number of MR dramatically dropped during the “first wave”, an early recovery was observed. Treatment prescriptions suffered a slight quantitative decrease during 2020, whereas substantial qualitative changes were found in specific treatments.
Published: 2022

2. Treatment response scoring systems to assess long-term prognosis in self-injectable DMTs relapsing-remitting multiple sclerosis patients

Author: Georgina Arrambide, Angela Vidal-Jordana, Ingrid Galán, Jaume Sastre-Garriga, Xavier Montalban, Susana Otero-Romero, Luca Prosperini, Manuel Comabella, Álvaro Cobo, Joaquim Castilló, Luciana Midaglia, Carlos Nos, Alex Rovira, Carmen Tur, Ana Zabalza, Breogán Rodríguez-Acevedo, Mar Tintoré, Jordi Río, Claudio Gasperini, and Cristina Auger
Subjects: medicine.medical_specialty, Treatment response, Neurology, Multiple Sclerosis, business.industry, Multiple sclerosis, medicine.disease, Prognosis, Predictive value, Magnetic Resonance Imaging, Multiple Sclerosis, Relapsing-Remitting, Relapsing remitting, Predictive Value of Tests, Internal medicine, medicine, Brain mri, Humans, Neurology (clinical), Significant risk, business, Neuroradiology
Abstract: Different treatment response scoring systems in treated MS patients exist. The objective was to assess the long-term predictive value of these systems in RRMS patients treated with self-injectable DMTs. RRMS-treated patients underwent brain MRI before the onset of therapy and 12 months thereafter, and neurological assessments every 6 months. Clinical and demographic characteristics were collected at baseline. After the first year of treatment, several scoring systems [Rio score (RS), modified Rio score (MRS), MAGNIMS score (MS), and ROAD score (RoS)] were calculated. Cox-Regression and survival analyses were performed to identify scores predicting long-term disability. We included 319 RRMS patients. Survival analyses showed that patients with RS > 1 and RoS > 3 had a significant risk of reaching an EDSS of 4.0 and 6.0 The score with the best sensitivity (61%) was the RoS, while the MRS showed the best specificity (88%). The RS showed the best positive predictive value (42%) and the best accuracy (81%). The combined measures integrated into different scores have an acceptable prognostic value for identifying patients with long-term disability. Thus, these data reinforce the concept of early treatment optimization to minimize the risk of long-term disability.
Published: 2021

3. Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis

Author: Regine Buffels, Stephen L. Hauser, Hideki Garren, Caroline Papeix, Jian Han, Ludwig Kappos, Xavier Montalban, Benjamin Turner, Damian Fiore, Jerry S. Wolinsky, and Bruce A.C. Cree
Subjects: Adult, Male, medicine.medical_specialty, Neurology, Adolescent, Post hoc, Opera, Gadolinium, Antibodies, Monoclonal, Humanized, Phase 3, Multiple sclerosis, Disability Evaluation, Young Adult, 03 medical and health sciences, Multiple Sclerosis, Relapsing-Remitting, Sex Factors, Interferon β-1a, 0302 clinical medicine, Double-Blind Method, Internal medicine, Image Processing, Computer-Assisted, Humans, Immunologic Factors, Medicine, Ocrelizumab, 030212 general & internal medicine, Prior treatment, business.industry, Drug Administration Routes, Interferon-beta, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Treatment period, Subgroup, Relapsing, Female, Disease characteristics, Neurology (clinical), business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Objective: The efficacy and safety of ocrelizumab, versus interferon (IFN) β-1a, for the treatment of relapsing multiple sclerosis (RMS) from the identically designed OPERA I (NCT01247324) and OPERA II (NCT01412333) phase III studies has been reported; here we present subgroup analyses of efficacy endpoints from the pooled OPERA I and OPERA II populations. Methods: Patients with RMS were randomized to either ocrelizumab 600 mg administered by intravenous infusion every 24 weeks or subcutaneous IFN β-1a 44 µg three times per week throughout the 96-week treatment period. Relapse, disability, and MRI outcomes were analyzed for predefined and post hoc subgroups based on demographic and disease characteristics along with prior treatment using appropriate statistical tests to determine the treatment effect in subgroups and treatment-by-subgroup interactions. Results: The significant treatment benefit of ocrelizumab, versus IFN β-1a, observed in the overall OPERA I and OPERA II pooled populations was maintained across most subgroup strata for all endpoints, including annualized relapse rate, disability progression, and MRI outputs. Conclusions: The treatment effect of ocrelizumab versus IFN β-1a, measured by clinical and MRI outcomes, was maintained across most of the subgroups and strata of interest, and the pattern of treatment benefit across all subgroups was consistent with that from the pooled OPERA studies.
Published: 2019

4. Correction to: Impact of COVID-19 pandemic on frequency of clinical visits, performance of MRI studies, and therapeutic choices in a multiple sclerosis referral centre

Author: Alvaro Cobo-Calvo, Ana Zabalza, Jordi Río, Georgina Arrambide, Susana Otero-Romero, Paula Tagliani, Simón Cárdenas-Robledo, Mireia Castillo, Carmen Espejo, Marta Rodriguez, Pere Carbonell, Breogán Rodríguez, Luciana Midaglia, Ángela Vidal-Jordana, Carmen Tur, Ingrid Galan, Joaquín Castillo, Manuel Comabella, Carlos Nos, Cristina Auger, Mar Tintoré, Àlex Rovira, Xavier Montalban, and Jaume Sastre-Garriga
Subjects: Neurology, Neurology (clinical)
Published: 2022

5. Correction to: Treatment response scoring systems to assess long-term prognosis in self-injectable DMTs relapsing–remitting multiple sclerosis patients

Author: Jordi Río, Àlex Rovira, Claudio Gasperini, Mar Tintoré, Luca Prosperini, Susana Otero-Romero, Manuel Comabella, Ángela Vidal-Jordana, Ingrid Galán, Luciana Midaglia, Breogán Rodriguez-Acevedo, Ana Zabalza, Joaquim Castilló, Georgina Arrambide, Carlos Nos, Álvaro Cobo-Calvo, Carmen Tur, Cristina Auger, Jaume Sastre-Garriga, and Xavier Montalban
Subjects: Neurology, Neurology (clinical)
Published: 2021

6. Blood lymphocyte subsets identify optimal responders to IFN-beta in MS

Author: Susana Sainz de la Maza, Eulalia Rodríguez-Martín, Roberto Alvarez-Lafuente, J.C. Álvarez-Cermeño, Carmen Espejo, Xavier Montalban, Jordi Río, Luisa M. Villar, Noelia Villarrubia, Raquel Alenda, Lucienne Costa-Frossard, and Maria Inmaculada Dominguez-Mozo
Subjects: Adult, Male, 0301 basic medicine, medicine.medical_specialty, Multiple Sclerosis, Neurology, Antibodies, Statistics, Nonparametric, Flow cytometry, Cohort Studies, Disability Evaluation, 03 medical and health sciences, Basal (phylogenetics), 0302 clinical medicine, Immune system, Antigens, CD, medicine, Humans, Immunologic Factors, Lymphocyte Count, Beta (finance), biology, medicine.diagnostic_test, Perforin, business.industry, Multiple sclerosis, Interferon-beta, Flow Cytometry, medicine.disease, Magnetic Resonance Imaging, Lymphocyte Subsets, Treatment Outcome, 030104 developmental biology, Immunology, biology.protein, Cytokines, Female, Neurology (clinical), Antibody, business, 030217 neurology & neurosurgery
Abstract: Response to interferon-beta (IFN-beta) treatment is heterogeneous in multiple sclerosis (MS). We aimed to search for biomarkers predicting no evidence of disease activity (NEDA) status upon IFN-beta treatment in MS. 119 patients with relapsing-remitting MS (RRMS) initiating IFN-beta treatment were included in the study, and followed prospectively for 2 years. Neutralizing antibodies (NAb) were explored in serum samples obtained after 6 and 12 months of IFN-beta treatment. Soluble cytokines and blood lymphocytes were studied in basal samples by ELISA and flow cytometry, respectively. 9% of patients developed NAb. These antibodies were more frequent in patients receiving IFN-beta 1b than in those treated subcutaneous (p = 0.008) or intramuscular (p
Published: 2017

7. Long-term results from a phase 2 extension study of fingolimod at high and approved dose in relapsing multiple sclerosis

Author: Malika Cremer, Xavier Montalban, Paul O'Connor, Ana de Vera, Philipp von Rosenstiel, Giancarlo Comi, Jack P. Antel, Ludwig Kappos, and Nikolaos Sfikas
Subjects: medicine.medical_specialty, Expanded Disability Status Scale, Fingolimod Hydrochloride, business.industry, Multiple sclerosis, Phases of clinical research, medicine.disease, Placebo, Magnetic Resonance Imaging, Fingolimod, Discontinuation, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, Neurology, Internal medicine, Outcome Assessment, Health Care, Physical therapy, medicine, Humans, Neurology (clinical), Adverse effect, business, Immunosuppressive Agents, medicine.drug
Abstract: Fingolimod safety and efficacy data in relapsing-remitting multiple sclerosis (RRMS) are available up to 5 years, from an extension of a randomized, placebo-controlled, double-blind, phase 2 study, at a dose higher (5.0/1.25 mg) than the approved dose of 0.5 mg. The objective of the study is to present the end-of-study data (>7 years) from the open-label extension of the phase 2 study. In the core phase (6 months), patients (N = 281) were randomized to placebo or fingolimod 1.25/5 mg. In the extension, placebo patients were randomized to fingolimod 1.25/5 mg. All patients received open-label 1.25 mg fingolimod after month 24 and 0.5 mg after month 60. Clinical visits were performed every 3 months, expanded disability status scale (EDSS) every 6 months and magnetic resonance imaging (MRI) annually. 122 (48.8%) patients completed the extension study; overall fingolimod exposure was 1230.7 patient-years. The most common (>10%) reasons for study discontinuation were adverse events (19.6%) and consent withdrawal (16.4%). Fingolimod treatment for >7 years was associated with sustained low clinical and MRI disease activity. Over 60% of patients remained relapse free and about 80% were free from any MRI activity. Overall annualized relapse rate was 0.18. Long-term fingolimod treatment was not associated with new safety concerns. Long-term fingolimod was well tolerated and associated with a sustained low level of disease activity.
Published: 2015

8. Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis

Author: Klaus Schmierer, M Wallner-Blazek, Frederik Barkhof, Charles Peter Tilbery, Hugo Pereira Pinto Gama, Tarek A. Yousry, José Flores, Christian Enzinger, Massimo Fillipp, Xavier Montalban, Jette L. Frederiksen, Alex Rovira, Antônio José da Rocha, Jacqueline Palace, David Miller, M A Rocca, Alexandra Seewann, Franz Fazekas, Achim Gass, Radiology and nuclear medicine, Neurology, NCA - Neuroinflamation, Wallner Blazek, M, Rovira, A, Filippi, Massimo, Rocca, Ma, Miller, Dh, Schmierer, K, Frederiksen, J, Gass, A, Gama, H, Tilbery, Cp, Rocha, Aj, Florez, J, Barkhof, F, Seewann, A, Palace, J, Yousry, Ta, Montalban, X, Enzinger, C, Fazekas, F, and on behalf of the MAGNIMS, Group
Subjects: Adult, Male, medicine.medical_specialty, Pathology, Multiple Sclerosis, Neurology, Adolescent, Databases, Factual, Gastroenterology, Lesion, Young Adult, Sex Factors, Internal medicine, medicine, Humans, Young adult, Neuroradiology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Age Factors, Clinical course, Brain, Magnetic resonance imaging, Polyradiculoneuropathy, Middle Aged, Prognosis, medicine.disease, Magnetic Resonance Imaging, Polyradiculoneuropathy, Chronic Inflammatory Demyelinating, Disease Progression, Female, Neurology (clinical), medicine.symptom, business, Follow-Up Studies
Abstract: Atypical lesions of a presumably idiopathic inflammatory demyelinating origin present quite variably and may pose diagnostic problems. The subsequent clinical course is also uncertain. We, therefore, wanted to clarify if atypical idiopathic inflammatory demyelinating lesions (AIIDLs) can be classified according to previously suggested radiologic characteristics and how this classification relates to prognosis. Searching the databases of eight tertiary referral centres we identified 90 adult patients (61 women, 29 men; mean age 34 years) with ≥1 AIIDL. We collected their demographic, clinical and magnetic resonance imaging data and obtained follow-up (FU) information on 77 of these patients over a mean duration of 4 years. The AIIDLs presented as a single lesion in 72 (80 %) patients and exhibited an infiltrative (n = 35), megacystic (n = 16), Baló (n = 10) or ring-like (n = 16) lesion appearance in 77 (86 %) patients. Additional multiple sclerosis (MS)-typical lesions existed in 48 (53 %) patients. During FU, a further clinical attack occurred rarely (23-35 % of patients) except for patients with ring-like AIIDLs (62 %). Further attacks were also significantly more often in patients with coexisting MS-typical lesions (41 vs. 10 %, p < 0.005). New AIIDLs developed in six (7 %), and new MS-typical lesions in 29 (42 %) patients. Our findings confirm the previously reported subtypes of AIIDLs. Most types confer a relatively low risk of further clinical attacks, except for ring-like lesions and the combination with MS-typical lesions. © 2013 Springer-Verlag Berlin Heidelberg.
Published: 2013

9. Treatment of cognitive impairment in multiple sclerosis: position paper

Author: Alan J. Thompson, Lauren B. Krupp, Ralph H.B. Benedict, Maria Pia Amato, Dawn Langdon, John DeLuca, Giancarlo Comi, Xavier Montalban, Amato, Mp, Langdon, D, Montalban, X, Benedict, Rh, Deluca, J, Krupp, Lb, Thompson, Aj, and Comi, Giancarlo
Subjects: medicine.medical_specialty, Multiple Sclerosis, business.industry, Interferon beta-1a, Cognition, Fingolimod, Clinical trial, Natalizumab, Physical medicine and rehabilitation, Neurology, medicine, Humans, Neurology (clinical), Cognitive rehabilitation therapy, Cognitive decline, Cognition Disorders, business, Donepezil, medicine.drug, Clinical psychology
Abstract: Cognitive impairment in multiple sclerosis (MS) is common, debilitating and burdensome. Key evidence from trials was reviewed to enable recommendations to be made to guide clinical practice and research. Behavioural and pharmacological interventions on cognition reported in published studies were reviewed. Most studies evaluating behavioural treatment for impairment in learning and memory, deficits of attention and executive function have demonstrated some improvement. Controlled studies in relapsing remitting MS indicate interferon (IFN) β-1b and IFN β-1a were associated with modest cognitive improvement. The effects of symptomatic therapies such as modafinil and donepezil are inconsistent. Most studies yielding positive findings have significant methodological difficulties limiting the confidence in making any broad treatment recommendations. There are no published reports of glatiramer acetate, natalizumab and fingolimod being effective in improving cognition in controlled trials. The effects of disease modifying therapies in other forms of MS and clinically isolated syndrome have not yielded positive results. Data linking behavioural therapy, symptomatic treatment or disease modifying treatment, to either reducing cognitive decline or improving impaired cognition are limited and inconsistent. The treatment and prevention of cognitive impairment needs to remain a key research focus, identifying new interventions and improving clinical trial methodology.
Published: 2012

10. Induction of serum soluble tumor necrosis factor receptor II (sTNF-RII) and interleukin-1 receptor antagonist (IL-1ra) by interferon beta-1b in patients with progressive multiple sclerosis

Author: Ana Rovira, Luis Brieva, Cristina López, Xavier Montalban, N. Téllez, Eva Julià, Manuel Comabella, José Antonio del Río, and Mar Tintoré
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, medicine.medical_treatment, Statistics as Topic, Enzyme-Linked Immunosorbent Assay, Interleukin-1 receptor, Receptors, Tumor Necrosis Factor, Etanercept, Proinflammatory cytokine, Adjuvants, Immunologic, Double-Blind Method, Internal medicine, medicine, Humans, Analysis of Variance, business.industry, Multiple sclerosis, Interferon beta-1b, Interferon-beta, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Interleukin 1 Receptor Antagonist Protein, Interleukin 1 receptor antagonist, Endocrinology, Cytokine, Neurology, Immunoglobulin G, Interleukin-21 receptor, Female, Neurology (clinical), business, Blood sampling
Abstract: Cytokine inhibitors, such as soluble tumor necrosis factor receptor II (sTNFRII) and interleukin-1 receptor antagonist (IL-1ra) are possible regulators of proinflammatory cytokine activity. Although previous studies have shown induction of sTNF-RII and IL-1ra by interferon-beta (IFNbeta) in patients with relapse-onset forms of multiple sclerosis (MS), to date no studies of these cytokine inhibitors have been performed in patients with essentially progressive forms of MS.To address the effects of IFNbeta on serum levels of sTNF-RII and IL-1ra in a cohort of progressive MS patients and to assess the relationship between levels and changes of sTNF-RII and IL-1ra and clinical and radiological variables. Methods Serial blood samples were obtained from a cohort of 73 patients with progressive MS who participated in a placebo-controlled clinical trial with IFNbeta-1b. Serum levels of sTNF-RII and IL-1ra were measured by multiplex enzyme-linked immunosorbent assay at baseline and after 3, 6, 12, and 24 months. EDSS and MSFC scores were recorded at the time of blood sampling, and MR scans were obtained at baseline and after 12 and 24 months.Treatment with IFNbeta was associated with significant increases of sTNF-RII and IL-1ra serum levels during the followup period. A strong correlation at 24 months was observed between levels of sTNF-RII and EDSS scores in the placebo group. Finally, a trend for negative association was found between changes in sTNFRII and percentage change in T2-weighted lesion load at 24 months in the IFNbeta treated group.sTNF-RII and IL-1ra levels are increased in the serum of progressive MS patients during IFNbeta therapy and may be one mechanism by which IFNbeta mediates its effects in the treatment of MS.
Published: 2008

11. Treating relapsing-remitting multiple sclerosis: therapy effects on brain atrophy

Author: Jaume Sastre-Garriga, Alex Rovira, Angela Vidal-Jordana, and Xavier Montalban
Subjects: Oncology, medicine.medical_specialty, Neurology, business.industry, Multiple sclerosis, Central nervous system, Brain, Disease, medicine.disease, Clinical trial, Atrophy, medicine.anatomical_structure, Multiple Sclerosis, Relapsing-Remitting, Internal medicine, Brain size, Medicine, Humans, Observational study, Neurology (clinical), business, Neuroscience
Abstract: Multiple sclerosis (MS) is an immune-mediated disease of the central nervous system with a complex and heterogeneous pathology that may ultimately lead to neurodegeneration and brain atrophy. Brain volume loss in MS is known to occur early in the disease course and to be clinically relevant, as it has been related to disability progression. Nowadays, brain volume loss is relatively easy to measure with different automated, reproducible and accurate software tools. Therefore, most of (if not all) the newest clinical trials have incorporated brain volume outcomes as a measure of treatment effect. With this review, we aimed to update and summarize all existing data regarding brain volume and RRMS treatment in clinical trials as well as in open-label observational studies of drugs with positive results in its primary outcome in at least one phase III trial as of March 2014.
Published: 2015

12. The importance of long-term data in multiple sclerosis

Author: Xavier Montalban
Subjects: medicine.medical_specialty, Pediatrics, Neurology, Clinically isolated syndrome, business.industry, Multiple sclerosis, medicine.disease, Natural history, Clinical trial, Cohort, Physical therapy, Medicine, Optic neuritis, Neurology (clinical), business, Natural history study
Abstract: ■ Abstract Natural history studies provide important information on the prognosis of multiple sclerosis and on risk factors for long-term outcome and thus help orientate treatment decisions and design clinical trials. Before the introduction of disease-modifying treatment, large longitudinal natural history studies described the typical clinical course of multiple sclerosis and identified landmark events in disease progression, for example that 50 % of patients with relapsing-remitting multiple sclerosis are unable to walk unaided 15 years after disease onset. A large observational natural history study performed in Barcelona following outcome after the first presentation with a clinically isolated syndrome revealed that patients presenting initially with optic neuritis were less likely to progress to clinically definite multiple sclerosis than other patients. This finding could be explained by a lower lesion load on cranial MRI. Initial lesion load also appeared to be an important determinant of future disability. These and other similar data suggest that the development of lesions early in the disease process has an important influence on long-term disability. Since the advent of disease-modifying treatments in multiple sclerosis, this natural history can also help define criteria for determining treatment failure. An analysis of a cohort of patients treated with β-interferons revealed that progression of EDSS disability scores during the first two years of treatment could predict treatment failure at six years (three points worsening in EDSS score since treatment initiation) with an accuracy of 92 %. Early progression of EDSS scores was itself associated with early accumulation of lesion load visible on MRI. Rate of accumulation of lesion load after first symptom presentation may thus be a useful marker of poor prognosis that could be considered an indicator of the need for intensive treatment. Initial long-term outcome data obtained with immunomodulatory treatments is consistent with the notion that these treatments improve the long-term prognosis. If this is confirmed, then a first step towards the goal of limiting irreversible disability in patients with multiple sclerosis will have been made.
Published: 2006

13. TNF–α converting enzyme (TACE) protein expression in different clinical subtypes of multiple sclerosis

Author: Juan C. Leza, María A. Moro, Montse Camiña, Manuel Comabella, H Perkal, Xavier Montalban, Cristina Romera, Ignacio Lizasoain, and Mireia Castillo
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, medicine.medical_treatment, Blotting, Western, Statistics as Topic, Gene Expression, Enzyme-Linked Immunosorbent Assay, ADAM17 Protein, Peripheral blood mononuclear cell, Gastroenterology, Central nervous system disease, Pathogenesis, Western blot, Internal medicine, Leukocytes, medicine, Humans, Immunologic Factors, medicine.diagnostic_test, business.industry, Multiple sclerosis, Interferon-beta, Middle Aged, medicine.disease, Blot, ADAM Proteins, Cytokine, Neurology, Immunology, Female, Tumor necrosis factor alpha, Neurology (clinical), business
Abstract: Tumor necrosis factor (TNF)-alpha converting enzyme (TACE, also called ADAM17) is a key sheddase that releases TNF-alpha from its inactive cell-bound precursor. TACE protein expression levels in peripheral blood mononuclear cells were measured by Western blot analysis in 20 healthy controls and 80 multiple sclerosis (MS) patients before and after treatment with IFNbeta [20 patients with primary progressive (PP) MS, 20 patients with secondary progressive (SP) MS, and 40 patients with relapsing- remitting (RR) MS (20 patients during clinical remission and 20 patients in relapse)]. TNF-alpha serum levels were also measured by enzyme-linked immunoassay in the MS patients and healthy controls. TACE protein expression levels were lower in healthy controls and PPMS patients compared with SPMS patients and RRMS patient during clinical remission. No differences in TACE protein levels were observed between RRMS patients in relapse and during remission. TACE protein levels were increased in PPMS patients treated with IFNbeta. Serum TNF-alpha levels were higher in RRMS patients in relapse compared with RRMS patients during remission, and positive and negative correlations were found between TACE protein expression and serum TNF-alpha levels in RRMS patients during relapse and during remission respectively. These findings point to different regulatory mechanisms of the TACE-TNF-alpha pathway in the clinical MS subtypes and expand the role of TACE in MS pathogenesis.
Published: 2006

14. Interferon beta in relapsing–remitting multiple sclerosis

Author: N. Téllez, Mar Tintoré, Jordi Río, Carlos Nos, Xavier Montalban, and Ingrid Galán
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Disability Evaluation, Multiple Sclerosis, Relapsing-Remitting, Adjuvants, Immunologic, Internal medicine, Secondary Prevention, medicine, Humans, Adverse effect, Survival analysis, Demography, Retrospective Studies, business.industry, Drug Administration Routes, Multiple sclerosis, Interferon beta-1b, Interferon beta-1a, Retrospective cohort study, Interferon-beta, medicine.disease, Survival Analysis, Surgery, Clinical trial, Neurology, Cohort, Female, Neurology (clinical), business, Follow-Up Studies, medicine.drug
Abstract: Long-term observational studies may provide additional information about the behaviour of different drugs in the post-marketing period. We present the data of our cohort of relapsing-remitting multiple sclerosis (RRMS) patients treated with interferon beta (IFNbeta).We analysed RRMS patients followed for at least 2 years. From 1995, we initiated therapy with IFNbeta. As they became available, patients were allocated to one of the IFNs at standard doses (IFNbeta-1b, IFNbeta-1a i.m. or IFNbeta-1a s.c.). Each patient was included in a follow-up protocol containing demographic and baseline clinical data.Between 1995 and 2004, 382 patients have completed at least 2 years of follow-up. Significant differences at entry were observed. Patients on IFNbeta-1b had a higher disease activity and disability at baseline than those on IFNbeta-1a i.m. or IFNbeta-1a s.c. A significant reduction in the relapse rate was observed for the three drugs (70% for IFNbeta-1b, 64% for IFNbeta-1a i.m. and 74% for IFNbeta-1a s.c.). We observed a sustained progression of disability in 11% of patients on IFNbeta-1b, 17% on IFNbeta-1a i.m. and 19% on IFNbeta-1a s.c.; and at four years of follow-up in 24% of patients on IFNbeta-1b, 23% on IFNbeta-1a i.m. and 35% on IFNbeta-1a s.c. No unexpected major adverse events were observed with any of the drugs.Interferon beta is safe and well tolerated. The various registered interferon beta drugs provide a comparable efficacy in a large non-selected cohort of RRMS patients.
Published: 2005

15. Correction to: Blood lymphocyte subsets identify optimal responders to IFN-beta in MS

Author: Jordi Río, Roberto Alvarez-Lafuente, Eulalia Rodríguez-Martín, J.C. Álvarez-Cermeño, Carmen Espejo, Luisa M. Villar, Lucienne Costa-Frossard, Raquel Alenda, Maria Inmaculada Dominguez-Mozo, Noelia Villarrubia, Susana Sainz de la Maza, and Xavier Montalban
Subjects: medicine.medical_specialty, Neurology, business.industry, Immunology, MEDLINE, Medicine, Neurology (clinical), business, Beta (finance), Blood lymphocyte, Neuroradiology
Abstract: The author claims that his name is incorrectly listed on PubMed. It seems that the first and last name has been mixed up.
Published: 2017

16. Radiologic MS disease activity during natalizumab treatment interruption: findings from RESTORE

Author: Ludwig Kappos, Jérôme De Seze, Amy Pace, Denise Campagnolo, Douglas Jeffery, Bianca Weinstock-Guttman, Petra Duda, Michael Kaufman, Robert J. Fox, Barry Ticho, Hans-Peter Hartung, Xavier Montalban, Ralf Gold, and Bruce A.C. Cree
Subjects: Adult, medicine.medical_specialty, Neurology, Multiple Sclerosis, Clinical Trials and Supportive Activities, Clinical Sciences, Treatment interruption, Relapsing-Remitting, Placebo, Gastroenterology, law.invention, Natalizumab, Multiple Sclerosis, Relapsing-Remitting, Randomized controlled trial, law, Clinical Research, Recurrence, Internal medicine, medicine, Humans, Gadolinium-enhancing lesions, Neuroradiology, Cancer, Neurology & Neurosurgery, business.industry, Multiple sclerosis, Medical record, Neurosciences, Evaluation of treatments and therapeutic interventions, medicine.disease, Magnetic Resonance Imaging, Surgery, Radiography, 6.1 Pharmaceuticals, Biomedical Imaging, Female, Neurology (clinical), business, medicine.drug, MRI
Abstract: The objective of this study is to characterize the timing and extent of radiologic MS disease recurrence during the 24-week natalizumab treatment interruption period in RESTORE. RESTORE was a randomized, partially placebo-controlled exploratory study. Natalizumab-treated patients with no gadolinium-enhancing (Gd+) lesions at screening (n = 175) were randomized 1:1:2 to continue natalizumab (n = 45), switch to placebo (n = 42), or switch to other therapies (n = 88) for 24 weeks. MRI assessments were performed every 4 weeks. Predictors of increased numbers of Gd+ lesions during natalizumab treatment interruption were evaluated. The numbers of Gd+ lesions were compared with retrospectively collected pre-natalizumab MRI reports and data from placebo-treated patients from two historical randomized clinical trials. Gd+ lesions were detected in 0 % (0/45) of natalizumab patients, 61 % (25/41) of placebo patients, and 48 % (39/81) of other-therapies patients during the randomized treatment period. Gd+ lesions were detected starting at week 12; most were observed at week 16 or later. Thirteen percent (14/107) of patients had >5 Gd+ lesions on ≥1 (of 6) scans during the randomized treatment period versus 7 % (7/107) of patients pre-natalizumab (based on medical record of a single scan). Younger patients and those with more Gd+ lesions pre-natalizumab were more likely to have increased MRI activity. Distribution of total and persistent Gd+ lesions in RESTORE patients was similar to placebo-treated historical control patients. In most patients, recurring radiological disease activity during natalizumab interruption did not exceed pre-natalizumab levels or levels seen in historical control patients.
Published: 2014

17. Clinically definite multiple sclerosis after radiological Schilder-like onset

Author: Ana Rovira, Xavier Montalban, M. Tintoré, José Antonio del Río, Jaume Sastre-Garriga, and E. Grivé
Subjects: medicine.medical_specialty, Neurology, business.industry, Multiple sclerosis, Radiological weapon, medicine, Neurology (clinical), Radiology, business, medicine.disease, Neuroradiology
Published: 2003

18. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain

Author: H. Hattig, C. Delli Pizzi, M. C. Addonizio, Michelle Davis, A. R. Giovagnoli, L. Florensa, M. Roth, J. de Kruijk, Francisco Lacruz, Ph. Dewailly, A. Toygar, C. Avendano, P.P. De Deyn, J. F. Hurtevent, F. Lomeila, T. W. Wong, Gordon T. Plant, M. Bud, H. J. Willison, DH Miller, D. W. Langdon, R. Cioni, J. Servan, A. Kaygisiz, E. Racadot, D. B. Schens, E. Picciola, L. Falip, C. Bouchard, J. Jotova, A. Jorge-Santamaria, P. Misra, A. Dufour, C. P. Panagopoulos, A. Venneri, B. Sredni, B. Angelard, M. Janelidze, M. Carreno, J. Obenberger, J. Pouget, H. W. Moser, R. Kaufmann, J. A. Molina, D. Linden, A. Martin Urda, E. Uvestad, A. Krone, J. P. Cochin, J. Mallecourt, A. Cambon-Thomsen, K. Violleau, P. Osschmann, A. M. Durocher, E. Bussaglia, D. M. Danielle, H. Efendi, C. Van Broeckhoven, K. G. Jordan, W. Rautenberg, C. Iniguez, J. M. Delgado, Graham Watson, M. Lawden, Gareth J. Barker, K. Stiasny, James T. Becker, G. Campanella, E. Peghi, A. Poli, A. Haddad, T. Yamawaki, Giacomo P. Comi, S. Sotgiu, B. Ersmark, A. Pomes, M. Ziegler, P. Ferrante, P. Ruppi, H. KuÇukoglu, R. Bouton, U. K. Rinne, P. Vieregge, M. Dary, P. Giunti, Peter J. Goadsby, S. Jung, E. Secor, A. Steinberg, N. Vila, M. A. Hernandez, M. Cursi, A. Enqelhardt, A. Engelhardt, J. Veitch, F. Di Silverio, F. Arnaud, B. Neundörfer, R. Brucher, Dominique Caparros-Lefebvre, B. Meyer, Marianne Dieterich, M. H. Snidaro, R. Gomez, R. Cerbo, M. Ragno, J. M. Vance, S. Nemni, A. Caliskan, F. Barros, I. Velcheva, D. Ceballos-Baumann, V. Barak, A. Avila, N. Antonova, F. Resche, S. Pappata, L. Varela, S. R. Silveira Santos, A. Cammarota, L. Naccache, Y. Nara, E. Tournier-Lasserves, R. Mobner, T. Chase, A. Ensenyat, J. Ulrich, G. Giegerich, M. Rother, M. Revilla, N. Nitschke, K. Honczarenko, E. Basart Tarrats, J. Blin, B. Jacob, J. Santamaria, S. Knezevic, J. L. Castillo, M. Antem, J. Colomer, O. Busse, Didier Hannequin, S. Carrier, J. B. Ruidavets, C. Rozman, J. Bogoussslavsky, J. Pascual Calvet, E. Monros, J. M. Polo, M. Zucconl, Javier Muruzabal, R. R. Allen, R. Rivolta, K. Haugaard, A. Nespolo, K. Hoang-Xuang, G. Bussone, T. Avramidis, E. Corsini, Christiana Franke, T. Vinogradova, H. Boot, K. Vestergaard, G. H. Jansen, N. Argentino, M. Raltzig, W. Linssen, Mark B. Pepys, P. Roblot, L. Lauritzen, E. Fainardi, D. Morin, T. X. Arbizu Urdiain, J. Wollenhaupt, S. Bostantjopoulou, G. Pavesi, A. D. Forman, Giovanni Fabbrini, D. Jean, J. J. Archelos, M. I. Blanchs, M. Del Gobbo, Anna Carla Turconi, Ch. Derouesné, Elio Scarpini, A. Visbeck, P. Castejon, J. P. Renou, F. Mounier-Vehier, G. Potagas, Ch. Duyckaerts, A. Filla, R. Schneider, G. Ronen, K. Nagata, J. P. Vedel, A. Henneberg, G. van Melle, C. Baratti, H. Knott, M. C. Prevett, A. Bes, B. Metin, Jos V. Reempts, L. Martorell, Mefkure Eraksoy, H. O. Handwerker, D. S. Younger, O. Oktem, D. Frongillo, C. Soriano-Soriano, L. Niehaus, F. Zipp, A. Tartaro, S Newman, R. H. Browne, P. Davous, R. Sanchez, M. Muros, M. E. Kornhuber, A. Lavarone, M. Mohr, M. R. Garcia, S. Russell, H. Kellar-Wood, M. R. Tola, B. Ostermeyer, Ch. Tzekov, K. Sartor, E. B. Ringelstein, P. P. Gazzaniga, Paul Krack, H. Fidaner, H. Rico, T. Dbaiss, F. Alameda, E. Torchiana, L. Rumbach, I. Charques, J. M. Bogaard, C. D. Frith, L. J. Rappelle, R. Brenner, A. Joutel, K. Fuxe, G. HÄcker, M. J. Blaser, J. Valls-SolÇ, G. Ulm, M. Alberdi, A. Bock, F. W. Bertelsmann, U. Wieshmann, J. Visa, J. R. Lupski, D. D'Amico, L. M. P. Ramos, A. A. Vanderbark, R. Horn, M. Warmuth, Dietmar Kühne, Mark S. Palmer, C. Ehrenheim, E. Canga, S. Viola, O. Scarpino, P. Naldi, R. Almeida, A. A. Raymond, J. Gamez, Stephan Arnold, A. DiGiovanni, J. Dalmau, C. C. Chari, H. F. Beer, J. C. Koetsier, J. Iriarte, E. Yunis, J. Casadevall, E. Le Guern, E. Stenager, S. R. Benbadis, J. M. Warter, F. Burklin, I. Theodorou, L. Johannesen, G. A. Graveland, X. Leclerc, I. Vecchio, L. Ozelius, G. Nicoletti, R. K. Gherardi, E. Esperet, M. L. Delodovici, F. Cattin, F. Paiau, Giorgio Sacilotto, C. A. J. Broere, D. Chavdarov, J. P. Willmer, C. H. Hawkes, Th. Naegele, E. Ellie, E. Dartigues, M. J. Guardiola, S. Hesse, Z. Levic, Marco Rovaris, P. Saugeir-Veber, B. A. Yaqub, H. F. Durwen, R. Larumbe, J. Ballabrina, M. Sendtner, J. Röther, M. Horstink, C. Kluglein, M.P. Montesi, H. Apaydin, J. Montoya, E. Waubant, Ch. Verellen-Dunoulin, A. Nicolai, J. Lopez-Delval, R. Lemon, G. Cantinho, E. Granieri, A. Zeviani, Wolfgang H. Oertel, U. Ficola, V. Di Piero, V. Fragola, K. Sabev, M. V. Guitera, I. Turki, F. Bolgert, P. Ingrand, J. M. Gobernado, L. M. E. Grimaldi, S. Baybas, B. Eymard, Y. Rolland, Y. Robitaille, Ta. Pampols, P. J. Koehler, A. Carroacedo, J. Vilchez, S. Di Vittorio, I. R. Rise, T. Nagy, M. Kuffner, E. Palazzini, A. Ott, J. Pruim, T. X. Arbizu, E. Manetti, C. Cervera, S. Felber, G. Gursoy, J. Scholz, G. A. Buscaino, M. S. Chen, A. Pascual, J. Hazan, J. U. Gajda, J. G. Cea, G. Bottini, G. Damalik, F. Le Doze, G. Bonaldi, J. M. Hew, C. Messina, A. M. Kennedy, J. M. Carney, N. M. F. Murray, M. Parent, M. Koepp, V. Dimova, D. De Leo, K. Jellinger, G. Salemi, S. Mientus, M. L. Hansen, F. Mazzucchelli, J. Vieth, M. Mauri, E. Bartels, L. Johannsen, C. Humphreys, J. Emile, D. N. Landon, E. Kansu, R. Sanchez-Pernaute, Rsj Frackowiak, M. Gonzalez Torres, L. Oller, C. Machedo, J. Kother, M. Billiard, H. Durak, T. Schindler, A. Frank, A. Uncini, A. Sbriccoli, C. Farinas, D. W. Paty, N. Fast, A. T. Zangaladze, A. Kerkhofs, J. M. Pino Garcia, I. De la Fuente, B. Marini, L. Gomez, I. Rubio, Alessandra Bardoni, C. Brodie, P. Acin, U. Sliwka, S. A. Hawkins, S. Tardieu, F. Vitullo, J. M. Pereira Monteino, R. Gagliardi, T. Jezewski, A. Cano, T. Lempert, F. Abad Alegria, G. Rotondo, D. Ince, C. Martinez Parra, Y. Huang, H. Luders, Y. Steinvil, F. G. A. Van Der Meche, R. Bianchi, A. Sanchez, T. Sevilla, J. M. Ketelslegers, A. Domzal-Stryga, M. Pandolfo, M. O. Josse, K. W. Neff, I. Blanco, G. W. Bruyn, O. W. Witte, J. L. Thibault, G. Andersen, J. Pariset, A. Marcone, R. J. M. Lane, A. Hofman, M. Verin, T. Matilla, P. Bedoucha, J. Roche, M. Lai, M. Collard, A. Ugarte, F. Gallecho, D. Silbersweig, C. Kennard, J. P. Azulay, T. W. Ho, P. L. I. Dellemijn, R. Girardello, F. Baas, B. Voss, F. Rozenberg, E. M. Brocker, V. Stanev, A. A. J. Soeterboek, A. Marra, A. Rey, E. Ertem, M. Sawradewicz-Rybak, J. De Keyser, P. Cavallari, F. Proust, Y. Chevalier, H. C. Hansen, D. Leys, C. A. Davie, K. Hoang-Xuan, C. Bairati, H. van Crevel, Thomas T. Warner, B. Bompais, A. Dobbeleir, T Campbell, C. Macko, C. J. M. Klijn, M. Dussallant, T. P. Berlit, W. Rozenbaum, M. J. van den Bent, W. A. Rocca, M. Muller, H. Hundemer, U. Zifko, M. Campera, F. Drislane, D. Ranoux, T. M. Kloss, Anil Kumar, I. Ruolt, C. Bargnani, B. Marescau, N. A. Losseff, S. Notermans, B. Kint, E. T. Burke, C. Aykut, J. Matias Guiu, P. Maquet, T. Drogendijk, M. Leone, K. von Ammon, M. Pepeliarska, C. Prados, L. DiGiamberardino, T. Logtenberg, G. Lenoir, I. Castaldo, Damhaut, M. Radionova, G. Sirabian, R. Navon, Giovanni Antonini, K. Al Moutaery, E. Chamas, R. Schönhuber, M. Giannini, B. Debilly, I. Labatut, H. Henon, J. A. Egido, M. Baudrimont, J. N. Lorenzo, J. E. C. Bromberg, R. Antonacci, J. J. Vilchez, T. Moulin, B. Rautenstrauss, Giovanni Meola, J. Noth, S Mammi, P. Laforet, F. Lopez, C. Gehring, S. Bort, G. Rancurel, D. Decamps, S. Kostadinova, Y. Shapira, B. Neundoerfer, D. Chavrot, M. Solimena, J. P. Salier, W. Deberdt, R. Hoff-Jörgensen, A. Messina, S. Meairs, G. Rosoklija, E. Nelis, I. Bertran, C. Ertekin, J. Lohmeyer, Mitermayer Galvao dos Reis, L. Calo, E. Maccagnano, A. P. Hays, J. Verlooy, M. G. Forno, T. Blanco, L. Bail, Gabriella Silvestri, J. Montero, F. Bertrand, R. T. Ghnassia, C. Besses, T. Sereghy, F. Shalit, G. Bogliun, S. Braghi, St. Baykouchev, C. Franke, A. Lasa, L. C. Archard, J. Kriebel, S. Shaunak, M. Nocito, Alexander Tsiskaridze, E. Manfredini, T. Seigal, David G. Gadian, M. Barlas, J. D. Degos, C. Seeber, J. Caemert, J. L. Mas, R. B. Pepinsky, M. G. D'Angelo, N. Baumann, S. Yorifuji, H. P. Endtz, M. A. Cassatella, R. A. C. Hughes, V. Golzi, A. Bittencourt, A. Ferreira, M. Sanson, C. Alper, M. Vermeulen, M. A. A. van Walderveen, E. Alexiou, C. H. Lucas, M. Fiorelli, Y. N. Debbink, R. Gil, S. Congia, T. Banerjee, J. M. Bouchard, A. N. Pinto, A. Ceballos-Baumann, G. Grollier, P. I. M. Schmitz, M. D. Catata, N. Lahat, N. S. Rao, P. Papathanasopoulos, J. Valls-Solé, D. Claus, G. Schroter, A. Castro, C. Videbaek, R. Martinez Dreke, A. D. Platts, M. Hermesl, A. C. PeÇanha-Martins, M. Cardoso Silva, P. Masnou, M. J. A. Tanner, Ch. Confavreux, B. Mishu, H. Rasmussen, L. Valenciano, Carlo Pozzilli, S. W. Li, V. Salzman, Y. Vashtang, Massimo Franceschi, M. Severo, G. Deuschl, S. Setien, G. Mariani, A. Protti, J. Castillo, M. J. B. Taphoorn, M. Frontali, I. Milonas, D. Decoq, J. A. Navarro, S. Castellvi-Pel, C. Ertikin, M. Urtasun, Y. Lajat, B. E. Kendall, E. Verdu, B. Gueguen, E. Boisen, R. Couderc, A Danek, JM Stevens, F. Nicoli, L. Feltri, M. L. Vazquez-Andre, J. A. Morgan-Hughes, L. D'Angelo, F. Y. Liew, L. F. Pascual, J. Patrignani Ochoa, Vittorio Martinelli, J. Cophignon, L. Zhang, S. Martin, J. F. Meder, H. C. Buschmann, L. Bertin, J. van Gijn, A. Barreiro, A. Cools, C. Leon, A. Berod, E. A. Anllo, E. Zanette, L. Petrov, R. Barona, B. Gallicchio, P. J. Cozzone, N. Diederich, G. Cancel, L. Schelosky, P. Orizaola, K. Yulug, S. Ozer, Valeria A. Sansone, B. Guiraud-Chaumeil, K. Voigt, P. Labauge, M. Eoli, J. Zhu, J. Aguirre, M. Ferrarini, B. Zyluk, E. Planas, A. Cadilha, C. Tortorella, H. Bismuth, C. E. Counsell, A. Laun, A. Ferlini, Rio J. Montalban, N. Biary, L. Becker, M. Fardeau, M. Poloni, V. M. S. de Bruin, C. Fornada, J. Barros, E. Ganzmann, E. Touze, D. Wallach, J. Peila, H. Fujimura, M. T. Iba-Zizen, G. Macchi, C. Villoslada, R. Gouider, Ph. Rondepierre, P. Grummich, P. Chiodi, C. Conte, M. Michels, P. Annunziata, G. Semana, C. Sommer, J. Vajsar, D. Zekin, J. Kulisevsky, David G. Munoz, B. Jacotot, M. Magoni, A. Luxen, T. Garcia-Silva, S. Di Cesare, Christophe Tzourio, M. Gomori, I. Picomell, L. Santoro, F. Villa, Giovanni Pennisi, T. Ribalta, J. M. Molto, L. Marzorati, P. Loiseau, F. Gemignani, A. Gironell, J. Wissel, A. Prusinski, F. Cailloux, P. Villanueva-Hemandez, P. Cozzone, T. Del Ser, J. Sans-Sabrafen, M. Zappia, P. W. A. Willems, G. Tchernia, D. Gardeur, R. Bauer, F. Palomo, H. Metz, S. Lamoureux, C. Chastang, I. Reinhard, A. Goldfarb, S. Harder, Jordi Río, C. Ozkara, E. Tekinsoy, P. Vontobell, J. De Recondo, M. Rabasa, L. Lacomblez, F. Boon, Dgt Thomas, V. Palma, Renato Mantegazza, A. Dervis, M. Nueckel, B. YalÇinerner, I. Duran, G. Dalla Volta, A. Zubimendi, J. Pinheiro, A. Marbini, Xavier Montalban, H. Wekerle, X. Pereira Monteino, F. Crespo, F. Koskas, N. Battistini, C. Ruiz, H. Offner, J. de Pommery, P. Kanovsky, J. Y. Barnett, J. Pardo, G. Tomei, R. Rene, H. M. Lokhorst, P. Thajeb, H. Bilgin, D. McGehee, R. Fahsold, L. Morgante, Katie Sidle, C. Delwaide, M. N. Diaye, P. H. Rice, A. Creange, C. Sabev, K. Stephan, K. WeilBenborn, G. Magnani, L. Grymonprez, F. Cardellach, M. Kaps, N. G. Meco, F. Vega, V. Bonifati, A. Desomer, M. Baldy-Moulinier, G. Kvale, F. J. Authier, B. Yegen, T. Ho, J. M. Rozet, E. A. Cabanis, L. Bruce, L. Ambrosoli, M. A. Petrella, M. Hernandez, P. Timmings, H. B. van der Worp, F. Mahieux, A. Urbano-Marquez, D. A. Krendel, A. A. Garcia, R. Divari, R. Michalowicz, M. R. Piedmonte, M. Bondavalli, M. Zanca, P. F. Ippel, Onofre Combarros, B. Tavitian, E. Hirsch, I. Anastasopoulos, A. Roses, A. Köhler, P. Vienna, V. Timmerman, P. Sergi, F. Cornelio, A. Di Pasquale, R. Verleger, S. Castellvirel, J. Proano, B. van Moll, F. Rubio, W. Hacke, I. Lavenu, L. Zetta, M. W. Tas, N. Bittmann, M. Bonamini, O. R. Hommes, V. Dousset, N. Afsar, S. Belal, R. R. Myers, J. Goes, Giuseppe Vita, E. Clementi, V. G. Karepov, M. Jueptner, A Vincent, P. Emmrich, Th. Heb, A. Caballo, J. Gallego, T. Mokrusch, C. Perla, L. Gebuhrer, O. Titlbach, Alessandro Prelle, A. Czlonkowska, M. Russo, D. Hadjiev, T. S. Chkhikvishvili, M. Oehlschlager, G. Becker, I. Günther, E. N. Stenager, J. Garcia Agundez, J. Casademont, J. Batlle, S. Podobnik-Sarkanji, C. Alonso-Villaverde, B. Delaguillaume, B. Genc, B. Mazoyer, A. Rodriguez-Al-barino, Ch. Hilger, B. Ferrero, R. Price, W. Grisold, L. Fuhry, D. Oulbani, D. Ewing, A. Petkov, W. Walther, A. Gokyigit, John Newsom-Davis, J. Tayot, D. Seliak, G. Pelliccioni, D. Campagne, K. Kessler, F. Boureau, D. Perani, J. P. N'Guyen, N. Tchalucova, B. A. Antin-Ozerkis, C. Lacroix, B. D. Aronovich, I. H. Jenkins, E. A. dos Reis, M. Hortells, H. M. Meinck, H. Ch. Buschmann, S. C. J. M. Jacobs, T. Wetter, P. Creissard, N. Martinez, J. Weidenfeldl, H. J. Sturenburg, G. Damlacik, V. Gracia, J. C. Turpin, A. Pou-Serradell, J. P. Vincent, T. Gagoshidze, U. Ozkutlu, M. McLeod, K. Siegfried, I. Tchaoussoglou, J. Hildebrand, S. Kowalska, M. C. Picot, G. Galardin, L. Crevits, F. Andreetta, S. Larumbe-Lobalde, G. de la Sierra, J. C. Alvarez-Cermeno, R. J. Seitz, P. L. Oey, L. Ptacek, A. M. J. Paans, A. Wirrwar, A. Schmied, J. Uilchez, H. Tounsi, D. Hipola, V. Avoledo, Y. Hirata, P. Vermersch, T. M. Aisonobe, J. Valls-SoIè, H. Staunton, J. Dichgans, R. Karabudak, I. Dones, G. Porta, E. Janssens, Maria Martinez, J. M. Fernandez-Real, R. Villagra, Y. Yoshino, C. Kabus, K. Schimrigk, I. Girard-Buttaz, F. Piccoli, F. Aichner, P. Zuchegna, S. M. Al Deeb, F. Bono, N. Busquets, A. Jobert, Patrizia Ciscato, M. Martin, L. Polman, S. Darbra, V. Le Cam-Duchez, F. Baldissera, B. Baykan-Kurt, D. Guez, M. Bratoeva, H. Matsui, M. Mila, H. Perron, L. Bjorge, G. Husby, Steven T. DeKosky, D. R. Cornblath, J. M. Gabriel, J. J. Poza, Y. Wu, A. Toscano, R. P. Kleyweg, J. Kuhnen, S. O. Confort-Gouny, A. Barcelo, A. M. Conti, C. Fiol, C. Steichen-Wiehn, J. Rodes, M. Cavenaile, C. Vedeler, M. Drlicek, C. Argentino, M. L. Peris, A. Cervello, A. Z. GinaÏ, S. Yancheva, D. Passingham, S. Aoba, D. L. Lopez, T. Rechlin, K. Sonka, L. Grazzi, V. Folnegovic-Smalc, Maurizio Moggio, S. Rivaud, F. G. I. Jennekens, C. H. Hartard, H. Meierkord, G. Stocklin, M. D. Catala, W. C. McKay, E. Salmon, C. Navarro, I. Pastor, L. Canafoglia, M. De Braekeleer, P. K. Thomas, C. Mocellini, C. Pierre-Jerome, M. C. Dalakas, P. Pollak, M. Levivier, Niall Quinn, G. E. Rivolta, Z. Tunca, H. Zeumer, J. Garcia Tena, St. Guily, P. Gaudray, Johannes Kornhuber, V. Petrunjashev, R. Montesanti, R. J. Abbott, H. Petit, G. Kiteva-Trencevska, F. Carletto, C. Ramo, I. M. Pino, P. Beau, G. F. Mennuni, F. Moschian, F. Meneghini, B. Zdziarska, B. Fontaine, C. Stephens, G. Meco, K. Reiners, G. Badlan, M. Sessa, I. Degaey, S. M. Hassan, C. Albani, F. Caroeller, M. Schroeder, G. Savettieri, A. Novelletto, R. Kurita, P. Oschmann, I. Plaza, M. Oliveres, Simone Spuler, A. Molins, M. Schwab, J. R. Kalden, C. P. Gennaula, Y. Baklan, O. Picard, J. M. Léger, B. Mokri, E. Ghidoni, M. Jacob, D. Deplanque, W. JÄnisch, C. De Andres, P. De Deyn, G. Guomundsson, B. Herron, J. Barado, J. L. Gastaut, Guglielmo Scarlato, F. Poron, Nicola Jones, H. Teisserenc, C. P. Hawkins, A. J. Steck, H. C. Chandler, S. Blanc, J. H. Faiss, Jm. Soler Insa, I. Sarova-Ponchas, M. Malberin, A. Sackmann, G. De Vuono, K. Kaiser-Rub, K. Badhia, E. Szwabowska-Orzeszko, S. Ramm, C. Jodice, G. Franck, J. Marta-Moreno, R. Sciolla, C. Fritz, A. Attaccalite, F. Weber, E. Neuman, M. Cannata, A. Rodriguez, I. Nachainkin, R. Raffaele, T. S. Yu, N. Losseff, E. Fabrizio, C. Khati, M. Keipes, M. P. Ortega, M. Ramos-Alvarez, E. Brambilla, A. Tarasov, K. H. Wollinsky, O. B. Paulson, F. Boller, G. Bozzato, H. Wagnur, R. Canton, D. Testa, E. Kutluaye, M. Calopa, D. Smadja, G. Malatesta, F. Baggi, A. Stracciari, G. Daral, G. Avanzini, J. Perret, J. Arenas, P. Boon, I. Gomes, A. Vortmeyer, P. Cesaro, S. Venz, E. Bernd Ringelstein, N. Milani, D. Laplane, P. Seibel, E. Tournier-Lasserve, Alexis Brice, L. Motti, E. Wascher, R. J. Abbot, F. Miralles, A. Turon, P. De Camilli, G. Luz, G. C. Guazzi, S. Tekin, F. Lesoin, T. Kryst, N. Lannoy, F. Gerstenbrand, S. Ballivet, H. A. M. van Diemen, J. Lopez-ArLandis, P. Bell, A. Silvani, M. A. Garcia, S. Vorstrup, D. Langdon, S. Ueno, B. Sander, V. Ozurk, C. Gurses, P. Berlit, J. M. Martinez-Lage, M. Treacy, S. O. Rodiek, S. Cherninkova, J. Grimaud, P. Marozzi, K. Hasert, S. Goldman, S. H. Ingwersen, A. Taghavy, T. Roig, R. Harper, I. Sarova-Pinchas, Anthony H.V. Schapira, R. Lebtahi, A. Vidaller, B. Stankov, D. Link, J. p. Malin, V. Petrova, Ludwig Kappos, J. L. Ochoa, T. Torbergsen, M. Carpo, M. Donato, Simon Shorvon, J. Mieszkowski, J. Perez-Serra, Raymond Voltz, G. Comi, S. Rafique, A. Perez-Sempere, N. Khalfallah, S. Bailleul, M. Borgers, S. Banfi, S. Mossman, A. Laihinen, G. Filippini, R. A. Grunewald, E. Stern, H. D. Herrmann, A. G. Droogan, P. Xue, A. Grilo, L. La Mantia, J. H. J. Wokke, S. Pizzul, Kie Kian Ang, S. Rapaport, W. Szaplyko, B. Romero, P. Brunet, A. 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Navasa, J. Ballabriga, G. Broggi, T. Gudeva, C. Rose, J. Vion-Dury, J. A. Gastaut, J. Pniewski, Nicola J. Robertson, G. Kohncke, M. Billot, S. Gok, E. Castellli, F. Denktas, P. Bazzi, F. Spinelli, I. F. Moseley, C. D. Mardsen, B. Barbiroli, O. M. Koriech, A. Miller, Hiroaki Yoshikawa, F. X. Borruat, J. Zielasek, P. Le Coz, J. Pascual, A. Drouet, L. T. Giron, F. Schondube, R. Midgard, M. Alizadeh, M. Liguori, Lionel Ginsberg, L. Harms, C. Tilgner, G. Tognoni, F. Molteni, Mar Tintoré, M. Psylla, C. Goulon-Goeau, M. V. Aguilar, Massimo Filippi, K. H. Mauritz, Thomas V. Fernandez, C. Basset, S. Rossi, P. Meneses, B. Jandolo, T. Locatelli, D. Shechtcr, C. Magnani, R. Ferri, Bruno Dubois, J. M. Warier, S. Berges, F. Idiman, M. Schabet, R. R. Diehl, P. D'aurelio, M. Musior, Reinhard Hohlfeld, P. Smeyers, M. Olivé, A. Riva, C. A. Broere, N. Egund, S. Franceschetti, V. Bonavita, Nicola Canal, E. Timmermans, M. Ruiz, S. Barrandon, G. Vasilaski, B. Deweer, L. Galiano, S. F. T. M. de Bruijn, L. Masana, A. Goossens, B. Heye, K. Lauer, Heinz Gregor Wieser, Stephen R. Williams, B. Garavaglia, A. P. Sempere, F. Grigoletto, P. Poindron, R. Lopez-Pajares, I. Leite, T. A. McNell, C. Caucheteur, J. M. Giron, A. D. Collins, P. Freger, J. Sanhez Del Rio, D. A. Harn, K. Lindner, S. S. Scherer, G. Serve, M. Juncadella, X. Estivill, R. Binkhorst, M. Anderson, B. Tekinsoy, C. Sagan, T. Anastopoulos, G. Japaridze, S. Guillou, F. Erminio, Jon Sussman, P. G. Oomes, D. S. Rust, S. Mascheroni, O. Berger, M. Peresson, K. V. Toyka, T. W. Polder, M. Huberman, B. Arpaci, H. Ramtami, I. Martinez, Ph. Violon, P. P. Gazzaniga Pozzill, R. Ruda, P. Auzou, J. Parker, S. P. Morrissey, Jiahong Zhu, F. Rotondi, P. Baron, W. Schmid, P. Doneda, M. Spadaro, M. C. Nargeot, I. Banchs, J.S.P. van den Berg, R. Ferrai, M. Robotti, M. Fredj, Pedro M. Rodríguez Cruz, B. Erne, D. G. Piepgras, M. C. Arne-Bes, J. Escudero, C. Goetz, A. R. Naylor, M. Hallett, O. Abramsky, E. Bonifacio, L. E. Larsson, R. Pellikka, P. Valalentino, D. Guidetti, B. Buchwald, C. H. Lücking, D. Gauvreau, F. Pfaff, A. Ben Younes-Chennoufi, R. Kiefer, R. Massot, K. A. Hossmann, L. Werdelin, P. J. Baxter, U. Ziflo, S. Allaria, C. D. Marsden, M. Cabaret, S. P. Mueller, E. Calabrese, R. Colao, S. I. Bekkelund, M. Yilmaz, O. Oktem-Tanor, R. Gine, M. E. Scheulen, J. Beuuer, A. Melo, Z. Gulay, M. D. Have, C. Frith, D. Liberati, J. Gozlan, P. Rondot, Ch. Brunholzl, M. Pocchiari, J. Pena, L. Moiola, C. Salvadori, A. Cabello, T. Catarci, S. Webb, C. Dettmers, N. A. Gregson, Alexandra Durr, F. Iglesias, U. Knorr, L. Ferrini-Strambi, F. Kruggel, P. Allard, A. Coquerel, P. Genet, F. Vinuels, C. Oberwittler, A. Torbicki, P. Leffers, B. Renault, B. Fauser, C. Ciano, G. Uziel, J. M. Gibson, F. Anaya, C. Derouesné, C. N. Anagnostou, M. Kaido, W. Eickhoff, G. Talerico, M. L. Berthier, A. Capdevila, M. Alons, D. Rezek, E. Wondrusch, U. Kauerz, D. Mateo, M. A. Chornet, Holon, N. Pinsard, I. Doganer, E. Paoino, H. Strenge, C. Diaz, J. R. Brasic, W. Heide, I. Santilli, W. M. Korn, D. Selcuki, M. J. Barrett, D. Krieger, T. Leon, T. Houallah, M. Tournilhac, C. Nos, D. Chavot, F. Barbieri, F. J. Jimenez-Jimenez, J. Muruzabal, K. Poeck, A. Sennlaub, L. M. Iriarte, L. G. Lazzarino, C. Sanz, P. A. Fischer, S. D. Shorvon, R. Hoermann, F. Delecluse, M. Krams, O. Corabianu, F. H. Hochberg, Christopher J. Mathias, B. Debachy, C. M. Poser, L. Delodovici, A. Jimenez-Escrig, F. Baruzzi, F. Godenberg, D. Cucinotta, P. J. Garcia Ruiz, K. Maier-Hauff, P. R. Bar, R. Mezt, R. Jochens, S. Karakaneva, C. Roberti, E. Caballero, Joseph E. Parisi, M. Zamboni, T. Lacasa, B. Baklan, J. C. Gautier, J. A. Martinez-Matos, W. Pollmann, G. Thomas, L. Verze, E. Chleide, R. Alvarez Sala, I. Noel, E. Albuisson, O. Kastrup, S. I. Rapoport, H. J. Braune, H. Lörler, M. Le Merrer, A. Biraben, S. Soler, S. J. Taagholt, U. Meyding-Lamadé, K. Bleasdale-Barr, Isabella Moroni, Y. Campos, J. Matias-Guiu, G. Edan, M. G. Bousser, John B. Clark, J. Garcia de Yebenes, N. K. Olsen, P. Hitzenberger, S. Einius, Aj Thompson, Ch. J. Vecht, T. Crepin-Leblond, Klaus L. Leenders, A. Di Muzio, L. Georgieva, René Spiegel, K. Sabey, D. Ménégalli, J. Meulstee, U. Liszka, P. Giral, C. Sunol, J. M. Espadaler, A. D. Crockar, K. Varli, G. Giraud, P. J. Hülser, A. Benazzouz, A. Reggio, M. Salvatore, K. Genc, M. Kushnir, S. Barbieri, J. Ph. Azulay, M. Gianelli, N. Bathien, A. AlMemar, F. Hentati, I. Ragueneau, F. Chiarotti, R. C. F. Smits, A. K. Asbury, F. Lacruz, B. Muller, Alan J. Thompson, Gordon Smith, K. Schmidt, C. Daems Monpeun, Juergen Weber, A. Arboix, G. R. Fink, A. M. Cobo, M. Ait Kaci Ahmed, E. Gencheva, Israel-Biet, G. Schlaug, P. De Jonghe, Philip Scheltens, K. Toyka, P. Gonzalez-Porque, A. Cila, J. M. Fernandez, P. Augustin, J. Siclia, S. Medaglini, D. E. Ziogas, A. Feve, L. Kater, G. J. E. Rinkel, D. Leppert, Rüdiger J. Seitz, S. Ried, C. Turc-Carel, G. Smeyers, F. Godinho, M. Czygan, M. Rijntjes, E. Aversa, M. Frigo, Leif Østergaard, J. L. Munoz Blanco, A. Cruz-Matinez, J. De Reuck, C. Theillet, T. Barroso, V. Oikonen, Florence Lebert, M. Kilinc, C. Cordon-Cardon, G. Stoll, E. Thiery, F. Pulcinelli, J. Solski, M. Schmiegelow, L. J. Polman, P. Fernandez-Calle, C. Wikkelso, M. Ben Hamida, M. Laska, E. Kott, W. Sulkowski, C. Lucas, N. M. Bornstein, D. Schmitz, M. W. Lammers, A. de Louw, R. J. S. Wise, P. A. van Darn, C. Antozzi, P. Villanueva, P. H. E. Hilkens, C. Constantin, W. Ricart, A. Wolf, M. Gamba, P. Maguire, Alessandro Padovani, B. M. Patten, Marie Sarazin, H. Ackermann, L. Durelli, S. Timsit, Sebastian Jander, B. W. Scheithauer, G. Demir, J. P. Neau, P. Barbanti, A. Brand, N. AraÇ, V. Fischer-Gagnepain, R. Marchioli, G. Serratrice, C. Maugard-Louboutin, G. T. Spencer, D. Lücke, G. Mainardi, K. Harmant Van Rijckevorsel, G. B. Creel, R. Manzanares, Francesco Fortunato, A. May, J. Workman, K. Johkura, E. Fernandez, Carlo Colosimo, L. Calliauw, L. Bet, Félix F. Cruz-Sánchez, M. Dhib, H. Meinardi, F. Carrara, J. Kuehnen, C. Peiro, H. Lassmann, K. Skovgaard Olsen, A. McDonald, L. Sciulli, A. Cobo, A. Monticelli, B. Conrad, J. Bagunya, J. Benitez, V. Desnizza, B. Dupont, O. Delrieu, D. Moraes, J. J. Heimans, F. Garcia Rio, M. Matsumto, A. Fernandez, R. Nermni, R. Chalmers, M. J. Marchau, F. Aguado, P. Velupillai, P. J. Martin, P. Tassan, V. Demarin, A. Engelien, T. Gerriets, Comar, J. L. Carrasco, J. P. Pruvo, A. Lopez de Munain, D. Pavitt, J. Alarcon, Chris H. Polman, B. Guldin, N. Yeni, Hartmut Brückmann, N. Wilczak, H. Szwed, R. Causaran, G. Kyriazis, M. E. Westarp, M. Gasparini, N. Pecora, J. M. Roda, E. Lang, V. Scaioli, David R. Fish, D. Caputo, O. Gratzl, R. Mercelis, A. Perretti, G. Steimetz, I. Link, C. Rigoletto, A. Catafau, G. Lucotte, M. Buti, G. Fagiolari, A. Piqueras, C. Godinot, J. C. Meurice, Erodriguez J. Dominigo, F. Lionnet, H. Grzelec, David J. Brooks, P. M. G. Munro, F. X. Weilbach, M. Maiwald, W. Split, B. Widjaja-Cramer, V. Ozturk, J. Colas, E. Brizioli, J. Calleja, L. Publio, M. Desi, R. Soffietti, P. Cortinovis-Tourniaire, E. F. Gonano, G. Cavaletti, S. Uselli, K. Westerlind, H. Betuel, C. O. Dhiver, H. Guggenheim, M. Hamon, R. Fazio, P. Lehikoinen, A. Esser, B. Sadzot, G. Fink, Angelo Antonini, D. Bendahan, V. Di Carlo, G. Galardi, A. F. Boller, M. Aksenova, Del Fiore, V. de la Sayette, H. Chabriat, A. Nicoletti, A. Dilouya, M. L. Harpin, E. Rouillet, J. Stam, A. Wolters, M. R. Delgado, Eduardo Tolosa, G. Said, A. J. Lees, L. Rinaldi, A. Schulze-Bonhage, MA Ron, C. Lefebvre, E. W. Radü, R. Alvarez, M. L. Bots, P. Reganati, S. Palazzi, A. Poggi, N. J. Scolding, V. Sazdovitch, T. Moreau, E. Maes, M. A. Estelies, P. Petkova, Jose-Felix Marti-Masso, G De La Meilleure, N. Mullatti, M. Rodegher, N. C. Notermans, T. A. T. Warner, S. Aktan, J. P. Louboutin, L. Volpe, C. Scheidt, W. Aust, C. M. Wiles, U. Schneider, S. K. Braekken, W. R. Willems, K. Usuku, Peter M. Rothwell, C. Talamon, M. L. Sacchetti, A. Codina, M. H. Marion, A. Santoro, J. Roda, A. Bordoni, D. J. Taylor, S. Ertas, H. H. Emmen, J. Vichez, V. BesanÇon, R. E. Passingham, M. L. Malosio, A. Vérier, M. Bamberg, A. W. Hansen, E. Mostacero, G. Gaudriault, Marie Vidailhet, B. Birebent, K. Strijckmans, F. Giannini, T. Kammer, I. Araujo, J. Nowicki, E. Nikolov, A. Hutzelmann, R. Gherardi, J. Verroust, L. Austoni, A. Scheller, A. Vazquez, S. Matheron, H. Holthausen, J. M. Gerard, M. Bataillard, S. Dethy, V. H. Patterson, V. Ivanez, N. P. Hirsch, F. Ozer, M. Sutter, C. Jacomet, M. Mora, Bruno Colombo, A. Sarropoulos, T. H. Papapetropoulos, M. Schwarz, D. S. Dinner, N. Acarin, B. Iandolo, J. O. Riis, P. R. J. Barnes, F. Taroni, J. Kazenwadel, L. Torre, A. Lugaresi, I. L. Henriques, S. Pauli, S. Alfonso, Pedro Quesada, A. S. T. Planting, J. M. Castilla, Thomas Gasser, M. Van der Linden, A. Alfaro, E. Nobile-Orazio, G. Popova, W. Vaalburg, F. G. A. van der Mech, L. Williams, F. Medina, J. P. Vernant, J. Yaouanq, B. Storch-Hagenlocher, A. Potemkowski, R. Riva, M. H. Mahagne, M. Ozturk, Ve. Drory, N. Konic, C. Jungreis, A. Pou Serradell, J. L. Gauvrit, G. J. Chelune, S. Hermandez, T. Dingus, L. Hewer, Ch. Koch, M. N. Metz-Lutz, G. Parlato, M. Sinaki, Charles Pierrot-Deseilligny, H. C. Diener, J. Broeckx, J. Weill-Fulazza, M. L. Villar, M. Rizzo, O. Ganslandt, C. Duran, N. A. Fletcher, G. Di Giovacchino, Susan T. Iannaccone, C. Kolig, N. Fabre, H. A. Crockard, Rita Bella, M. Tazir, E. Papagiannuli, K. Overgaard, Emma Ciafaloni, I. Lorenzetti, F. Viader, P. A. H. Millac, I. Montiel, L. H. Visser, M. Palomar, P. L. Murgia, H. Pedersen, Rafael Blesa, S. Seddigh, W. O. Renier, I. Lemahieu, H. M. L. Jansen, L. Rosin, J. Galofre, K. Mattos, M. Pondal, G. M. Hadjigeorgiou, D. Francis, L. Cantin, D. Stegeman, M. Rango, A. B. M. F. Karim, S. Schraff, B. Castellotti, I. Iriarte, E. Laborde, T. J. Tjan, R. Mutani, D. Toni, B. Bergaasco, J. G. Young, C. Klotzsch, A. Zincone, X. Ducrocq, M. Uchuya, O. J. Kolar, A. Quattrone, T. Bauermann, Nereo Bresolin, J. Vallée, B. C. Jacobs, A. Campos, Werner Poewe, J. A. Villanueva, A. W. Kornhuber, A. Malafosse, E. Diez-Tejedor, G. Jungreia, M. J. A. Puchner, A. Komiyama, O. Saribas, V. Volpini, L. Geremia, S. Bressi, A. Nibbio, Timothy E. Bates, T. z. Tzonev, E. Ideman, G. A. Damlacik, G. Martino, G. Crepaldi, T. Martino, Kjell Någren, E. Idiman, D. Samuel, J. M. Perez Trullen, Y. van der Graaf, J. O. Thorell, M. J. M. Dupuis, E. Sieber, R. D'Alessandro, C. Cazzaniga, J. Faiss, A. Tanguy, A. Schick, I. Hoksergen, A. Cardozo, R. Shakarishvili, G. K. Wennlng, J. L. Marti-Vilalta, J. Weissenbach, I. L. Simone, Amalia C. Bruni, Darius J. Adams, C. Weiller, A. Pietrangeli, F. Croria, C. Vigo-Pelfrey, Patricia Limousin, A. Ducros, G. Conti, O. Lindvall, E. Richter, M. Zuffi, A. Nappo, T. Riise, J. Wijdenes, M. J. Fernandez, J. Rosell, P. Vermersh, S. Servidei, M. S. C. Verdugo, F. Gouttiere, W. Solbach, M. Malbezin, I. S. Watanabe, A. Tumac, W. I. McDonald, D. A. Butterfield, P. P. Costa, F. deRino, F. Bamonti, J. M. Cesar, C. H. Lahoz, I. Mosely, M. Starck, M. H. Lemaitre, K. M. Stephan, S. Tex, R. Bokonjic, I. Mollee, L. Pastena, M. Gutierrez, F. Boiler, M. C. Martinez-Para, M. Velicogna, O. Obuz, A. Grinspan, M. Guarino, L. M. Cartier, E. Ruiz, D. Gambi, S. Messina, M. Villa, Michael G. Hanna, J. Valk, Leone Pascual, M. Clanet, Z. Argov, B. Ryniewicz, E. Magni, B. Berlanga, K. S. Wong, C. Gellera, C. Prevost, F. Gonzalez-Huix, R. Petraroli, J. E. G. Benedikz, I. Kojder, C. Bommelaer, L. Perusse, M. R. Bangioanni, Guy M. McKhann, A. Molina, C. Fresquet, E. Sindern, Florence Pasquier, M. J. Rosas, M. Altieri, O. Simoncini, M. Koutroumanidis, C. A. F. Tulleken, M. Dary-Auriol, S. Oueslati, H. Kruyer, I. Nishisho, C. R. Horning, A. Vital, G. V. Czettritz, J. Ph. Neau, B. Mihout, A. Ameri, M. Francis, S. Quasthoff, D. Taussig, S. Blunt, P. Valentin, C. Y. Gao, O. Heinzlef, H. d'Allens, C. Coudero, M. Erfas, G. Borghero, P. J. Modrego Pardo, M. C. Patrosso, N. L. Gershfeld, P. A. J. M. Boon, O. Sabouraud, M. Lara, J. Svennevig, G. L. Lenzi, A. Barrio, H. Villaroya, JosÇ M. Manubens, O. Boespflug-Tanguy, M. Carreras, D. A. Costiga, J. P. Breux, S. Lynn, C. Oliveras Ley, A. G. Herbaut, J. Nos, C. Tornali, Y. A. Hekster, J. L. Chopard, J. M. Manubens, P. Chemouilli, A. Jovicic, F. Dworzak, S. Smirne, S. E. Soudain, B. Gallano, D. Lubach, G. Masullo, G. Izquierdo, A. Pascual Leone Pascual, A. Sessa, V. Freitas, O. Crambes, L. Ouss, G. W. Van Dijk, P. Marchettini, P. Confalonieri, M. Donaghy, A. Munnich, M. Corbo, and M. E. L. van der Burg
Subjects: Neurology, business.industry, Media studies, Library science, Medicine, Neurology (clinical), business
Published: 1994

19. Clinical features of CIS of the brainstem/cerebellum of the kind seen in MS

Author: Joaquín Castilló, Manuel Comabella, Xavier Montalban, Mar Tintoré, Ana Rovira, Carmen Tur, Jaume Sastre-Garriga, N. Téllez, Carlos Nos, José Antonio del Río, Alejandro Horga, and H Perkal
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Neurology, Multiple Sclerosis, Risk Factors, Cerebellum, medicine, Diplopia, Humans, Prospective Studies, Neuroradiology, Retrospective Studies, Dyskinesias, Gait Disturbance, Multiple sclerosis, Retrospective cohort study, McDonald criteria, Odds ratio, medicine.disease, Prognosis, Surgery, Disease Progression, Female, Neurology (clinical), medicine.symptom, Psychology, Brain Stem, Demyelinating Diseases, Follow-Up Studies
Abstract: Recognition of multiple sclerosis (MS) attacks relies mostly on clinical assessment. However, their definition based on McDonald criteria refers mostly to timing and when dealing with clinical features is rather ambiguous: "...of the kind seen in multiple sclerosis." This is heightened in clinically isolated syndromes of the brainstem/cerebellum (CISB), where clinical manifestations can be manifold. This study aimed to describe the clinical features of patients with CISB to improve clinical recognition of patients with brainstem manifestations at the onset of their MS. To this end, we conducted a retrospective analysis of case notes of consecutively recruited patients with CISB assessed within 3 months of symptoms onset. Seventy-five patients were included. Most common brainstem-specific symptoms were: diplopia (68%), facial sensory symptoms (32%) and gait disturbance (31%). Adjusting for follow-up times, total number of symptoms and presence of other brainstem-specific symptoms, only the presence of facial sensory symptoms was predictive of (a lower risk of) conversion to clinically definite (CD) MS (Odds ratio: 0.086; p = 0.007). Neither the total number of brainstem-specific, non brainstem-specific nor the sum of both predicted conversion to CDMS. Results indicate that diplopia, facial sensory symptoms and gait disturbance occur in more than 30% of patients with CISB. Facial sensory symptoms are less associated with conversion to CDMS.
Published: 2009

20. Interferon beta in secondary progressive multiple sclerosis : daily clinical practice

Author: Carlos Nos, Neus Téllez, Ingrid Galán, Jordi Río, Xavier Montalban, Raul Pelayo, and Mar Tintoré
Subjects: Adult, Male, medicine.medical_specialty, Neurology, Observation, Cohort Studies, Internal medicine, medicine, Humans, Immunologic Factors, Adverse effect, Survival analysis, Retrospective Studies, business.industry, Multiple sclerosis, Retrospective cohort study, Interferon-beta, Middle Aged, Multiple Sclerosis, Chronic Progressive, medicine.disease, Survival Analysis, Surgery, Clinical trial, Cohort, Regression Analysis, Female, Neurology (clinical), business, Cohort study
Abstract: Observational studies may provide additional information about the behaviour of different drugs in the post-marketing period. We present the data from a cohort of secondary progressive multiple sclerosis (SPMS) patients treated with interferon beta (IFNbeta-1b) at our MS clinic.This was an independent, open-label, non-randomised, observational study. Within the period 1998 to 2005, all patients with SPMS who started therapy with IFNbeta-1b at our centre were studied. Each patient was included in a follow-up protocol collecting demographic and baseline clinical data.We studied 146 SPMS patients with a median follow-up of 60 months. Over the total study period, 62.2% of patients had confirmed progression. The analysis of the time to con- firmed progression showed that patients with two or more relapses in the 2 years before IFNbeta initiation, had a higher risk of disability increase than those patients with less than two relapses (p = 0.002). Multiple regression analysis showed disease activity in terms of relapses as the only factor to predict increase of disability during the follow-up period. A significant proportion of patients (36%) stopped treatment during the follow-up period. IFNbeta was safe, although some unexpected adverse events were observed.A higher disease activity before the beginning of treatment with IFNbeta in SPMS patients with a given EDSS rank could identify those with faster disability progression after treatment initiation.
Published: 2006

21. Fatigue in multiple sclerosis persists over time: a longitudinal study

Author: Ingrid Galán, Mar Tintoré, N. Téllez, Xavier Montalban, José Antonio del Río, and Carlos Nos
Subjects: Adult, Male, medicine.medical_specialty, Longitudinal study, Neurology, Multiple Sclerosis, Time Factors, Central nervous system disease, Disability Evaluation, medicine, Humans, Longitudinal Studies, Depression (differential diagnoses), Fatigue, Psychiatric Status Rating Scales, Expanded Disability Status Scale, Depression, Multiple sclerosis, Beck Depression Inventory, medicine.disease, Mood, Physical therapy, Female, Neurology (clinical), Psychology
Abstract: Fatigue is one of the most frequent symptoms in multiple sclerosis (MS) but there is a lack of knowledge about its behaviour over time. The aim of our study was to investigate changes in fatigue in a large cohort of MS patients and to determine the relationship between changes in disability and depression with changes in fatigue severity. We studied fatigue in 227 MS consecutive patients and again after one year. During the clinical interview, we recorded the patient’s degree of disability using the Expanded Disability Status Scale and relapses; fatigue was measured by means of the Modified Fatigue Impact Scale (MFIS) and Fatigue Severity Scale (FSS) and depression was measured by the Beck Depression Inventory (BDI). After a mean follow-up of 18 months, 86.8% of patients who were fatigued at study onset remained in a fatigued status, whereas 25% of those without fatigue at onset had become fatigued at the end of follow-up. We observed that only variations on BDI scores positively correlate with variations on fatigue scales, mainly with MFIS (r = 0.49, p
Published: 2005

22. The pros and cons of early treatment of relapsing forms of multiple sclerosis

Author: Xavier Montalban
Subjects: First episode, Pediatrics, medicine.medical_specialty, Time Factors, Neurology, medicine.diagnostic_test, business.industry, Multiple sclerosis, Axonal loss, Magnetic resonance imaging, Interferon-beta, medicine.disease, Surgery, Clinical trial, Multiple Sclerosis, Relapsing-Remitting, Atrophy, Tolerability, medicine, Humans, Controlled Clinical Trials as Topic, Neurology (clinical), business
Abstract: Cerebral axonal damage and brain atrophy begin at the earliest stages of multiple sclerosis (MS). Progressive neuronal degeneration contributes to irreversible neurological deficit, and ultimately disability. Axonal loss, which seems to be related to the inflammatory process, occurs much more rapidly in the early than later phases of disease, providing additional impetus for early intervention. The CHAMPS (Controlled High risk Avonex MultiPle Sclerosis) and ETOMS (Early Treatment Of MS) studies show that fewer patients with a first demyelinating event and abnormal magnetic resonance imaging (MRI) had a second clinical attack within 2 years if once-weekly treatment with interferon beta-1a was started at the time of the first episode. However, these studies provide no information on long-term outcomes. The BENEFIT study (BEtaferon/betaseron in Newly Emerging multiple sclerosis For Initial Treatment) will evaluate the efficacy and tolerability of 250 micro g (8 MIU) interferon beta-1b administered every other day to patients with a first demyelinating event suggestive of MS. This study should add some information about some of the outstanding questions relating to the long-term effects of early treatment on disease course, although it is likely that further investigation will be needed before a definite picture can be obtained.
Published: 2004

23. Reversible white matter alterations in encephalopathy associated with autoimmune thyroid disease

Author: A. Cantón, Xavier Montalban, Patricia Pozo-Rosich, Alex Rovira, Pablo Villoslada, and Rafael Simó
Subjects: medicine.medical_specialty, Pathology, Neurology, Prednisolone, Encephalopathy, Anti-Inflammatory Agents, Disease, Methylprednisolone, Thyroiditis, White matter, Central nervous system disease, Diagnosis, Differential, medicine, Humans, Autoantibodies, Autoimmune disease, Brain Diseases, medicine.diagnostic_test, business.industry, Thyroiditis, Autoimmune, Magnetic resonance imaging, Middle Aged, medicine.disease, Magnetic Resonance Imaging, Radiography, Thyroxine, medicine.anatomical_structure, Female, Neurology (clinical), business
Abstract: Encephalopathy associated with autoimmune thyroid disease is an underdiagnosed clinical condition. No specific disease marker exists and to date, imaging techniques have not proven useful. The disease is characterized by seizures, stroke-like events and psychiatric symptoms. Here, we present the report of a patient with encephalopathy associated with autoimmune thyroid disease in which a reversible white matter disorder was detected by MR imaging. This encephalopathy was alleviated and later disappeared following corticosteroid treatment. We conclude that the white matter is the principal brain tissue involved in this condition and that brain MRI studies may prove to be a useful tool in the diagnosis of patients suffering this treatable disease.
Published: 2002

24. Lambert–Eaton Myasthenic syndrome associated with sarcoidosis

Author: Manuel Comabella, F. Purroy García, J. Majó, N. Raguer, and Xavier Montalban
Subjects: medicine.medical_specialty, Neurology, business.industry, medicine, Neurology (clinical), Sarcoidosis, medicine.disease, business, Lambert-Eaton myasthenic syndrome, Dermatology, Neuroradiology
Published: 2005

25. CSF 14-3-3 protein assay and MRI as prognostic markers in patients with a clinically isolated syndrome suggestive of MS

Author: Yolanda Blanco, Antonio Martínez-Yélamos, Xavier Montalban, M. Tintoré, Albert Saiz, Raquel Sánchez-Valle, Sergio Martínez-Yélamos, T. Arbizu, Ana Rovira, and Francesc Graus
Subjects: Pathology, medicine.medical_specialty, Clinically isolated syndrome, Neurology, medicine.diagnostic_test, business.industry, Magnetic resonance imaging, Medicine, In patient, Neurology (clinical), business, Chi-squared distribution, Bradford protein assay, 14-3-3 protein, Neuroradiology
Published: 2004

26. Serial gadolinium-enhanced MRI in acute attack of multiple sclerosis treated with plasma exchange

Author: Mar Tintoré, Xavier Montalban, I Pericot, Alex Rovira, M. Dolors Castellà, and Jordi Río
Subjects: Mitoxantrone, medicine.medical_specialty, Neurology, medicine.diagnostic_test, business.industry, Gadolinium, Multiple sclerosis, chemistry.chemical_element, Magnetic resonance imaging, medicine.disease, Central nervous system disease, Methylprednisolone, chemistry, medicine, Neurology (clinical), Nuclear medicine, business, Neuroradiology, medicine.drug
Published: 2003

27. Polyglandular autoimmune syndrome type II and multiple sclerosis

Author: Jaume Sastre-Garriga, Xavier Montalban, and M. Tintoré
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Neurology, Syndrome type, business.industry, Multiple sclerosis, medicine.disease, Dermatology, Autoimmune Diseases, Text mining, Prevalence, Humans, Medicine, Female, Neurology (clinical), Polyendocrinopathies, Autoimmune, business, Neuroradiology
Published: 2001

28. Lower motor neuron disease in a HIV-2 infected woman

Author: Jaume Sastre-Garriga, A Codina, M. Tintoré, Xavier Montalban, N. Raguer, and I Ruíz
Subjects: medicine.medical_specialty, Pediatrics, Neurology, medicine.diagnostic_test, business.industry, Human immunodeficiency virus (HIV), Electromyography, medicine.disease_cause, Text mining, X ray computed, medicine, Lower motor neuron disease, Neurology (clinical), business, Neuroradiology
Published: 2000

29. Reply to D. S. Goodin

Author: Xavier Montalban and Jordi Río
Subjects: Neurology, business.industry, Medicine, Neurology (clinical), Anatomy, business, Neuroradiology
Published: 2006

30. Early vocal cord paralysis in olivopontocerebellar atrophy

Author: A Codina, J. Serena, Xavier Montalban, Lozano M, and Manuel Comabella
Subjects: medicine.medical_specialty, Neurology, Olivopontocerebellar atrophy, business.industry, medicine, Neurology (clinical), Anatomy, Vocal cord paralysis, business, medicine.disease, Neuroradiology
Published: 1996

31. Natalizumab treatment of multiple sclerosis in Spain: results of an extensive observational study

Author: Xavier Montalban, Celia Oreja-Guevara, Guillermo Izquierdo, Oscar Fernandez, J. L. Pérez, and R. Arroyo
Subjects: Adult, Male, medicine.medical_specialty, Multiple Sclerosis, Clinical Neurology, Observation, Antibodies, Monoclonal, Humanized, Statistics, Nonparametric, Disability Evaluation, Young Adult, Natalizumab, Internal medicine, Observational study, medicine, Humans, Immunologic Factors, Relapse, Disability progression, Expanded Disability Status Scale, Original Communication, business.industry, Progressive multifocal leukoencephalopathy, Multiple sclerosis, medicine.disease, Confidence interval, Surgery, Discontinuation, Clinical trial, Neurology, Spain, Female, Neurology (clinical), business, medicine.drug
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
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31 results on '"Xavier Montalban"'

1. Impact of COVID-19 pandemic on frequency of clinical visits, performance of MRI studies, and therapeutic choices in a multiple sclerosis referral centre

2. Treatment response scoring systems to assess long-term prognosis in self-injectable DMTs relapsing-remitting multiple sclerosis patients

3. Ocrelizumab efficacy in subgroups of patients with relapsing multiple sclerosis

4. Correction to: Impact of COVID-19 pandemic on frequency of clinical visits, performance of MRI studies, and therapeutic choices in a multiple sclerosis referral centre

5. Correction to: Treatment response scoring systems to assess long-term prognosis in self-injectable DMTs relapsing–remitting multiple sclerosis patients

6. Blood lymphocyte subsets identify optimal responders to IFN-beta in MS

7. Long-term results from a phase 2 extension study of fingolimod at high and approved dose in relapsing multiple sclerosis

8. Atypical idiopathic inflammatory demyelinating lesions: prognostic implications and relation to multiple sclerosis

9. Treatment of cognitive impairment in multiple sclerosis: position paper

10. Induction of serum soluble tumor necrosis factor receptor II (sTNF-RII) and interleukin-1 receptor antagonist (IL-1ra) by interferon beta-1b in patients with progressive multiple sclerosis

11. Treating relapsing-remitting multiple sclerosis: therapy effects on brain atrophy

12. The importance of long-term data in multiple sclerosis

13. TNF–α converting enzyme (TACE) protein expression in different clinical subtypes of multiple sclerosis

14. Interferon beta in relapsing–remitting multiple sclerosis

15. Correction to: Blood lymphocyte subsets identify optimal responders to IFN-beta in MS

16. Radiologic MS disease activity during natalizumab treatment interruption: findings from RESTORE

17. Clinically definite multiple sclerosis after radiological Schilder-like onset

18. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain

19. Clinical features of CIS of the brainstem/cerebellum of the kind seen in MS

20. Interferon beta in secondary progressive multiple sclerosis : daily clinical practice

21. Fatigue in multiple sclerosis persists over time: a longitudinal study

22. The pros and cons of early treatment of relapsing forms of multiple sclerosis

23. Reversible white matter alterations in encephalopathy associated with autoimmune thyroid disease

24. Lambert–Eaton Myasthenic syndrome associated with sarcoidosis

25. CSF 14-3-3 protein assay and MRI as prognostic markers in patients with a clinically isolated syndrome suggestive of MS

26. Serial gadolinium-enhanced MRI in acute attack of multiple sclerosis treated with plasma exchange

27. Polyglandular autoimmune syndrome type II and multiple sclerosis

28. Lower motor neuron disease in a HIV-2 infected woman

29. Reply to D. S. Goodin

30. Early vocal cord paralysis in olivopontocerebellar atrophy

31. Natalizumab treatment of multiple sclerosis in Spain: results of an extensive observational study

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