Search

Your search keyword '"Deryck, Olivier"' showing total 48 results
Start Over Author "Deryck, Olivier"
48 results on '"Deryck, Olivier"'

1. Brain age as a biomarker for pathological versus healthy ageing – a REMEMBER study

Author

Wittens, Mandy M.J., Denissen, Stijn, Sima, Diana M., Fransen, Erik, Niemantsverdriet, Ellis, Bastin, Christine, Benoit, Florence, Bergmans, Bruno, Bier, Jean-Christophe, de Deyn, Peter Paul, Deryck, Olivier, Hanseeuw, Bernard, Ivanoiu, Adrian, Picard, Gaëtane, Ribbens, Annemie, Salmon, Eric, Segers, Kurt, Sieben, Anne, Struyfs, Hanne, Thiery, Evert, Tournoy, Jos, van Binst, Anne-Marie, Versijpt, Jan, Smeets, Dirk, Bjerke, Maria, Nagels, Guy, and Engelborghs, Sebastiaan

Published
2024
Full Text
View/download PDF

3. Clinical variability and onset age modifiers in an extended Belgian GRN founder family

Author

Goeman, Johan, Nuytten, Dirk, Vandenbulcke, Mathieu, Michotte, Alex, Salmon, Eric, Deryck, Olivier, Bergmans, Bruno, Willems, Christiana, Delbeck, Jean, Wauters, Eline, Van Mossevelde, Sara, Sleegers, Kristel, van der Zee, Julie, Engelborghs, Sebastiaan, Sieben, Anne, Vandenberghe, Rik, Philtjens, Stéphanie, Van den Broeck, Marleen, Peeters, Karin, Cuijt, Ivy, De Coster, Wouter, Van Langenhove, Tim, Santens, Patrick, Ivanoiu, Adrian, Cras, Patrick, De Bleecker, Jan L., Versijpt, Jan, Crols, Roeland, De Klippel, Nina, Martin, Jean-Jacques, De Deyn, Peter P., Cruts, Marc, and Van Broeckhoven, Christine

Published
2018
Full Text
View/download PDF

4. A Belgian consensus protocol for autologous hematopoietic stem cell transplantation in multiple sclerosis

Author

Laureys, Guy, Willekens, Barbara, Vanopdenbosch, Ludo, Deryck, Olivier, Selleslag, Dominik, D’Haeseleer, Miguel, De Becker, Ann, Dubois, Bénédicte, Dierickx, Daan, Perrotta, Gaetano, De Wilde, Virginie, van Pesch, Vincent, Straetmans, Nicole, Dive, Dominique, Beguin, Yves, Van Wijmeersch, Bart, Theunissen, Koen, Kerre, Tessa, and Van de Velde, Ann

Published
2018
Full Text
View/download PDF

5. Patients carrying the mutation p.R406W in MAPT present with non-conforming phenotypic spectrum

Author

Gossye, Helena, Van Mossevelde, Sara, Sieben, Anne, Bjerke, M., Hendrickx Van De Craen, Elisabeth, Van Der Zee, Julie, De Deyn, Peter Paul, De Bleecker, Jan, Versijpt, Jan, van den Ende, Jenneke, Deryck, Olivier, Bourgeois, Paul, Bier, Jean Christophe, Goethals, Maarten, Vandenberghe, Rik, Engelborghs, Sebastiaan, Van Broeckhoven, Christine, Gossye, Helena, Van Mossevelde, Sara, Sieben, Anne, Bjerke, M., Hendrickx Van De Craen, Elisabeth, Van Der Zee, Julie, De Deyn, Peter Paul, De Bleecker, Jan, Versijpt, Jan, van den Ende, Jenneke, Deryck, Olivier, Bourgeois, Paul, Bier, Jean Christophe, Goethals, Maarten, Vandenberghe, Rik, Engelborghs, Sebastiaan, and Van Broeckhoven, Christine

Abstract

The missense mutation p.R406W in microtubule-associated protein tau leads to frontotemporal lobar degeneration with an amnestic, Alzheimer's disease-like phenotype with an autosomal dominant pattern of inheritance. In 2003, we described the pedigree of a Belgian family, labelled ADG, with 28 p.R406W patients. Over 18 years follow-up, we extended the family with 10 p.R406W carriers and provided an in-depth clinical description of the patients. Additionally, genetic screening was used to identify p.R406W carriers in Belgian cohorts of frontotemporal dementia and Alzheimer's disease patients and to calculate p.R406W frequency. In the frontotemporal dementia cohort, we found four p.R406W carriers (n = 647, 0.62%) and three in the Alzheimer's disease cohort (n = 1134, 0.26%). Haplotype sharing analysis showed evidence of a shared haplotype suggesting that they are descendants of a common ancestor. Of the p.R406W patients, we describe characteristics of neuropsychological, imaging and fluid biomarkers as well as neuropathologic examination. Intriguingly, the phenotypic spectrum among the p.R406W patients ranged from typical behavioural variant frontotemporal dementia to clinical Alzheimer's disease, based on CSF biomarker analysis and amyloid PET scan. Heterogeneous overlap syndromes existed in between, with highly common neuropsychiatric symptoms like disinhibition and aggressiveness, which occurred in 100% of frontotemporal dementia and 58% of clinical Alzheimer's disease patients. This was also the case for memory problems, 89% in frontotemporal dementia and 100% in clinical Alzheimer's disease patients. Median age at death was significantly lower in patients with frontotemporal dementia (68 years) compared to clinical Alzheimer's disease patients (79 years), although the sizes of the sub-cohorts are limited and do not allow prognostic predictions. Post-mortem brain analysis of one p.R406W patient with behavioural variant frontotemporal dementia revealed frontotemporal, SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2023

6. Microtubule associated protein tau p.R406W patient carriers present with a nonconforming clinical phenotype

Author

Gossye, Helena, primary, Van Mossevelde, Sara, additional, Sieben, Anne, additional, Bjerke, Maria, additional, de Craen, Elisabeth Henndrickx Van, additional, van der Zee, Julie, additional, De Deyn, Peter Paul, additional, De Bleecker, Jan, additional, Versijpt, Jan, additional, Van den Ende, Jenneke, additional, Deryck, Olivier, additional, Bourgeois, Paul, additional, Bier, Jean‐Christophe, additional, Goethals, Maarten, additional, Engelborghs, Sebastiaan, additional, and Van Broeckhoven, Christine, additional

Published
2022
Full Text
View/download PDF

7. Alzheimer’s disease and driving: review of the literature and consensus guideline from Belgian dementia experts and the Belgian road safety institute endorsed by the Belgian Medical Association

Author

Versijpt, Jan, Tant, Mark, Beyer, Ingo, Bier, Jean-Christophe, Cras, Patrick, De Deyn, Peter P., De Wit, Patrick, Deryck, Olivier, Hanseeuw, Bernard, Lambert, Margareta, Lemper, Jean-Claude, Mormont, Eric, Petrovic, Mirko, Picard, Gaetane, Salmon, Eric, Segers, Kurt, Sieben, Anne, Thiery, Evert, Tournoy, Jos, Vandewoude, Maurits, Ventura, Manfredi, Verschraegen, Jurn, Engelborghs, Sebastiaan, Goffin, Tom, Deneyer, Michel, and Ivanoiu, Adrian

Published
2017
Full Text
View/download PDF

8. Patients carrying the mutation p.R406W in MAPT present with non-conforming phenotypic spectrum

Author

Gossye, Helena, primary, Van Mossevelde, Sara, additional, Sieben, Anne, additional, Bjerke, Maria, additional, Hendrickx Van de Craen, Elisabeth, additional, van der Zee, Julie, additional, De Deyn, Peter P, additional, De Bleecker, Jan, additional, Versijpt, Jan, additional, van den Ende, Jenneke, additional, Deryck, Olivier, additional, Bourgeois, Paul, additional, Bier, Jean-Christophe, additional, Goethals, Maarten, additional, Vandenberghe, Rik, additional, Engelborghs, Sebastiaan, additional, and Van Broeckhoven, Christine, additional

Published
2022
Full Text
View/download PDF

10. Frequent MAPT p.R406W Carriers with a Nonconforming FTD Phenotype in the Belgian Population (S20.006)

Author

Gossye, Helena, primary, Van Mossevelde, Sara, additional, Van Der Zee, Julie, additional, Sieben, Anne, additional, Bjerke, Maria, additional, Engelborghs, Sebastiaan, additional, De Deyn, Peter, additional, De Bleecker, Jan, additional, Versijpt, Jan, additional, Van Den Ende, Jenneke, additional, Deryck, Olivier, additional, Bourgeois, Paul, additional, Bier, Jean-Christophe, additional, Goethals, Maarten, additional, and Van Broeckhoven, Christine, additional

Published
2022
Full Text
View/download PDF

12. Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort

Author

Goeman, Johan, Nuytten, Dirk, Vandenbulcke, Mathieu, Santens, Patrick, De Bleecker, Jan, Sieben, Anne, Dermaut, Bart, Versijpt, Jan, Michotte, Alex, Deryck, Olivier, Bergmans, Bruno, Willems, Christiana, Ivanoiu, Adrian, Salmon, Eric, Alexopoulos, Panagiotis, Sorbi, Sandro, Bessi, Valentina, Bagnoli, Silvia, Santana, Isabel, Simões do Couto, Frederico, Martins, Madalena, Thonberg, Håkan, Fratiglioni, Laura, Padovani, Alessandro, Rohan, Zdenek, Razquin, Cristina, Lorenzo, Elena, Iglesias, Elena, Seijo-Martínez, Manuel, Rene, Ramon, Gascon, Jordi, Campdelacreu, Jaume, Koutroumani, Maria, Lleó, Alberto, Fortea, Juan, Blesa, Rafael, Verheijen, Jan, van der Zee, Julie, Gijselinck, Ilse, Van den Bossche, Tobi, Dillen, Lubina, Heeman, Bavo, Gómez-Tortosa, Estrella, Lladó, Albert, Sanchez-Valle, Raquel, Graff, Caroline, Pastor, Pau, Pastor, Maria A., Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, Clarimon, Jordi, de Mendonça, Alexandre, Gelpi, Ellen, Tsolaki, Magda, Diehl-Schmid, Janine, Nacmias, Benedetta, Almeida, Maria Rosário, Borroni, Barbara, Matej, Radoslav, Ruiz, Agustín, Engelborghs, Sebastiaan, Vandenberghe, Rik, De Deyn, Peter P., Cruts, Marc, Van Broeckhoven, Christine, and Sleegers, Kristel

Published
2018
Full Text
View/download PDF

13. NEK1 genetic variability in a Belgian cohort of ALS and ALS-FTD patients

Author

Engelborghs, Sebastiaan, Crols, Roeland, De Deyn, Peter P., De Jonghe, Peter, Baets, Jonathan, Cras, Patrick, Mercelis, Rudy, Vandenberghe, Rik, Sieben, Anne, Santens, Patrick, Ivanoiu, Adrian, Deryck, Olivier, Vanopdenbosch, Ludo, Delbeck, Jean, Nguyen, Hung Phuoc, Van Mossevelde, Sara, Dillen, Lubina, De Bleecker, Jan L., Moisse, Matthieu, Van Damme, Philip, Van Broeckhoven, Christine, and van der Zee, Julie

Published
2018
Full Text
View/download PDF

14. TBK1 Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author

van der Zee, Julie, Gijselinck, Ilse, Van Mossevelde, Sara, Perrone, Federica, Dillen, Lubina, Heeman, Bavo, Bäumer, Veerle, Engelborghs, Sebastiaan, De Bleecker, Jan, Baets, Jonathan, Gelpi, Ellen, RojasGarcía, Ricardo, Clarimón, Jordi, Lleó, Alberto, DiehlSchmid, Janine, Alexopoulos, Panagiotis, Perneczky, Robert, Synofzik, Matthis, Just, Jennifer, Schöls, Ludger, Graff, Caroline, Thonberg, Håkan, Borroni, Barbara, Padovani, Alessandro, Jordanova, Albena, Sarafov, Stayko, Tournev, Ivailo, de Mendonça, Alexandre, MiltenbergerMiltényi, Gabriel, Simões do Couto, Frederico, Ramirez, Alfredo, Jessen, Frank, Heneka, Michael T., GómezTortosa, Estrella, Danek, Adrian, Cras, Patrick, Vandenberghe, Rik, De Jonghe, Peter, De Deyn, Peter P., Sleegers, Kristel, Cruts, Marc, Van Broeckhoven, Christine, Goeman, Johan, Nuytten, Dirk, Smets, Katrien, Robberecht, Wim, Damme, Philip Van, Bleecker, Jan De, Santens, Patrick, Dermaut, Bart, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Delbeck, Jean, Bruyland, Marc, Willems, Christiana, Salmon, Eric, Pastor, Pau, OrtegaCubero, Sara, Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, Hernández, Isabel, Boada, Mercè, Ruiz, Agustín, Sorbi, Sandro, Nacmias, Benedetta, Bagnoli, Silvia, Sorbi, Sandro, SanchezValle, Raquel, Llado, Albert, Santana, Isabel, Rosário Almeida, Maria, Frisoni, Giovanni B, Maetzler, Walter, Matej, Radoslav, Fraidakis, Matthew J., Kovacs, Gabor G., Fabrizi, Gian Maria, and Testi, Silvia

Published
2017
Full Text
View/download PDF

15. Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients

Author

Nuytten, Dirk, Smets, Katrien, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Delbeck, Jean, Bruyland, Marc, Willems, Christiana, Salmon, Eric, Perrone, Federica, Nguyen, Hung Phuoc, Van Mossevelde, Sara, Moisse, Matthieu, Sieben, Anne, Santens, Patrick, De Bleecker, Jan, Vandenbulcke, Mathieu, Engelborghs, Sebastiaan, Baets, Jonathan, Cras, Patrick, Vandenberghe, Rik, De Jonghe, Peter, De Deyn, Peter P., Martin, Jean-Jacques, Van Damme, Philip, Van Broeckhoven, Christine, and van der Zee, Julie

Published
2017
Full Text
View/download PDF

16. Diagnostic performance of automated MRI volumetry by icobrain DM for Alzheimer's disease in a clinical setting: A REMEMBER study

Author

Wittens, Mandy M.J., primary, Sima, Diana M., additional, Houbrechts, Ruben, additional, Ribbens, Annemie, additional, Niemantsverdriet, Ellis, additional, Fransen, Erik, additional, Bastin, Christine, additional, Benoit, Florence, additional, Bergmans, Bruno, additional, Bier, Jean‐Christophe, additional, Deyn, Peter Paul, additional, Deryck, Olivier, additional, Hanseeuw, Bernard J., additional, Ivanoiu, Adrian, additional, Lemper, Jean‐Claude, additional, Mormont, Eric, additional, Picard, Gaëtane, additional, Salmon, Eric, additional, Segers, Kurt, additional, Sieben, Anne, additional, Smeets, Dirk, additional, Struyfs, Hanne, additional, Thiery, Evert, additional, Tournoy, Jos, additional, Triau, Eric, additional, Vanbinst, Anne‐Marie, additional, Versijpt, Jan, additional, Bjerke, Maria, additional, and Engelborghs, Sebastiaan, additional

Published
2021
Full Text
View/download PDF

17. Diagnostic Performance of Automated MRI Volumetry by icobrain dm for Alzheimer’s Disease in a Clinical Setting: A REMEMBER Study

Author

Wittens, Mandy Melissa Jane, primary, Sima, Diana Maria, additional, Houbrechts, Ruben, additional, Ribbens, Annemie, additional, Niemantsverdriet, Ellis, additional, Fransen, Erik, additional, Bastin, Christine, additional, Benoit, Florence, additional, Bergmans, Bruno, additional, Bier, Jean-Christophe, additional, De Deyn, Peter Paul, additional, Deryck, Olivier, additional, Hanseeuw, Bernard, additional, Ivanoiu, Adrian, additional, Lemper, Jean-Claude, additional, Mormont, Eric, additional, Picard, Gaëtane, additional, de la Rosa, Ezequiel, additional, Salmon, Eric, additional, Segers, Kurt, additional, Sieben, Anne, additional, Smeets, Dirk, additional, Struyfs, Hanne, additional, Thiery, Evert, additional, Tournoy, Jos, additional, Triau, Eric, additional, Vanbinst, Anne-Marie, additional, Versijpt, Jan, additional, Bjerke, Maria, additional, and Engelborghs, Sebastiaan, additional

Published
2021
Full Text
View/download PDF

18. Diagnostic Performance of Automated MRI Volumetry by icobrain dm for Alzheimer's Disease in a Clinical Setting: A REMEMBER Study.

Author

UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de neurologie, Wittens, Mandy Melissa Jane, Sima, Diana Maria, Houbrechts, Ruben, Ribbens, Annemie, Niemantsverdriet, Ellis, Fransen, Erik, Bastin, Christine, Benoit, Florence, Bergmans, Bruno, Bier, Jean-Christophe, De Deyn, Peter Paul, Deryck, Olivier, Hanseeuw, Bernard, Ivanoiu, Adrian, Lemper, Jean-Claude, Mormont, Eric, Picard, Gaëtane, de la Rosa, Ezequiel, Salmon, Eric, Segers, Kurt, Sieben, Anne, Smeets, Dirk, Struyfs, Hanne, Thiery, Evert, Tournoy, Jos, Triau, Eric, Vanbinst, Anne-Marie, Versijpt, Jan, Bjerke, Maria, Engelborghs, Sebastiaan, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de neurologie, Wittens, Mandy Melissa Jane, Sima, Diana Maria, Houbrechts, Ruben, Ribbens, Annemie, Niemantsverdriet, Ellis, Fransen, Erik, Bastin, Christine, Benoit, Florence, Bergmans, Bruno, Bier, Jean-Christophe, De Deyn, Peter Paul, Deryck, Olivier, Hanseeuw, Bernard, Ivanoiu, Adrian, Lemper, Jean-Claude, Mormont, Eric, Picard, Gaëtane, de la Rosa, Ezequiel, Salmon, Eric, Segers, Kurt, Sieben, Anne, Smeets, Dirk, Struyfs, Hanne, Thiery, Evert, Tournoy, Jos, Triau, Eric, Vanbinst, Anne-Marie, Versijpt, Jan, Bjerke, Maria, and Engelborghs, Sebastiaan

Abstract

Magnetic resonance imaging (MRI) has become important in the diagnostic work-up of neurodegenerative diseases. icobrain dm, a CE-labeled and FDA-cleared automated brain volumetry software, has shown potential in differentiating cognitively healthy controls (HC) from Alzheimer's disease (AD) dementia (ADD) patients in selected research cohorts. This study examines the diagnostic value of icobrain dm for AD in routine clinical practice, including a comparison to the widely used FreeSurfer software, and investigates if combined brain volumes contribute to establish an AD diagnosis. The study population included HC (n = 90), subjective cognitive decline (SCD, n = 93), mild cognitive impairment (MCI, n = 357), and ADD (n = 280) patients. Through automated volumetric analyses of global, cortical, and subcortical brain structures on clinical brain MRI T1w (n = 820) images from a retrospective, multi-center study (REMEMBER), icobrain dm's (v.4.4.0) ability to differentiate disease stages via ROC analysis was compared to FreeSurfer (v.6.0). Stepwise backward regression models were constructed to investigate if combined brain volumes can differentiate between AD stages. icobrain dm outperformed FreeSurfer in processing time (15-30 min versus 9-32 h), robustness (0 versus 67 failures), and diagnostic performance for whole brain, hippocampal volumes, and lateral ventricles between HC and ADD patients. Stepwise backward regression showed improved diagnostic accuracy for pairwise group differentiations, with highest performance obtained for distinguishing HC from ADD (AUC = 0.914; Specificity 83.0%; Sensitivity 86.3%). Automated volumetry has a diagnostic value for ADD diagnosis in routine clinical practice. Our findings indicate that combined brain volumes improve diagnostic accuracy, using real-world imaging data from a clinical setting.

Published
2021

20. Distinct Clinical Characteristics of C9orf72 Expansion Carriers Compared With GRN, MAPT, and Nonmutation Carriers in a Flanders-Belgian FTLD Cohort

Author

Van Langenhove, Tim, van der Zee, Julie, Gijselinck, Ilse, Engelborghs, Sebastiaan, Vandenberghe, Rik, Vandenbulcke, Mathieu, De Bleecker, Jan, Sieben, Anne, Versijpt, Jan, Ivanoiu, Adrian, Deryck, Olivier, Willems, Christiana, Dillen, Lubina, Philtjens, Stéphanie, Maes, Githa, Bäumer, Veerle, Van Den Broeck, Marleen, Mattheijssens, Maria, Peeters, Karin, Martin, Jean-Jacques, Michotte, Alex, Santens, Patrick, De Jonghe, Peter, Cras, Patrick, De Deyn, Peter P., Cruts, Marc, and Van Broeckhoven, Christine

Published
2013
Full Text
View/download PDF

21. Loss of DPP6 in neurodegenerative dementia: a genetic player in the dysfunction of neuronal excitability

Author

Cacace, Rita, Heeman, Bavo, Van Mossevelde, Sara, De Roeck, Arne, Hoogmartens, Julie, De Rijk, Peter, Gossye, Helena, De Vos, Kristof, De Coster, Wouter, Strazisar, Mojca, De Baets, Greet, Schymkowitz, Joost, Rousseau, Frederic, Geerts, Nathalie, De Pooter, Tim, Peeters, Karin, Sieben, Anne, Martin, Jean-Jacques, Engelborghs, Sebastiaan, Salmon, Eric, Santens, Patrick, Vandenberghe, Rik, Cras, Patrick, De Deyn, Peter P, van Swieten, John C, van Duijn, Cornelia M, van der Zee, Julie, Sleegers, Kristel, Van Broeckhoven, Christine, BELNEU Consortium, on behalf of the, Goeman, Johan, Crols, Roeland, Nuytten, Dirk, De Bleecker, Jan, Van Langenhove, Tim, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Versijpt, Jan, Michotte, Alex, Delbeck, Jean, Willems, Christiana, De Klippel, Nina, Neurology, Epidemiology, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/NEUR - Clinical Neuroscience, Faculty of Sciences and Bioengineering Sciences, Department of Bio-engineering Sciences, Clinical sciences, Physiotherapy, Human Physiology and Anatomy, and Pathologic Biochemistry and Physiology

Subjects
0301 basic medicine, Male, NATIONAL INSTITUTE, Potassium Channels, Action Potentials, Penetrance, neurodegenerative brain diseases, Synaptic Transmission, 0302 clinical medicine, C9orf72, Pathology, Medicine and Health Sciences, Homeostasis, BEHAVIORAL VARIANT, MUTATION, Genes, Dominant, Neurons, Medicine(all), Protein Stability, Neurodegeneration, Neurodegenerative Diseases, Frontotemporal lobar degeneration, ASSOCIATION, Middle Aged, Pedigree, ALZHEIMERS-DISEASE, PROTEIN DPPX, Protein Transport, Female, Life Sciences & Biomedicine, Chromosomes, Human, Pair 7, Frontotemporal dementia, Adult, Clinical Neurology, C9ORF72, Nerve Tissue Proteins, DPP6, Hyperexcitability, Biology, Polymorphism, Single Nucleotide, Pathology and Forensic Medicine, Frameshift mutation, Oxford nanopore technologies (ONT) PromethION, 03 medical and health sciences, Cellular and Molecular Neuroscience, medicine, Dementia, Humans, Dipeptidyl-Peptidases and Tripeptidyl-Peptidases, Loss function, Aged, Original Paper, FRONTOTEMPORAL LOBAR DEGENERATION, Science & Technology, Neurodegenerative brain diseases, Neurosciences, Biology and Life Sciences, medicine.disease, STRUCTURAL VARIATION, 030104 developmental biology, Whole genome sequencing, Chromosome Inversion, Mutation, Neurology (clinical), Neurosciences & Neurology, Human medicine, Neuroscience, 030217 neurology & neurosurgery, DENDRITIC EXCITABILITY, dementia
Abstract

Emerging evidence suggested a converging mechanism in neurodegenerative brain diseases (NBD) involving early neuronal network dysfunctions and alterations in the homeostasis of neuronal firing as culprits of neurodegeneration. In this study, we used paired-end short-read and direct long-read whole genome sequencing to investigate an unresolved autosomal dominant dementia family significantly linked to 7q36. We identified and validated a chromosomal inversion of ca. 4 Mb, segregating on the disease haplotype and disrupting the coding sequence of dipeptidyl-peptidase 6 gene (DPP6). DPP6 resequencing identified significantly more rare variants—nonsense, frameshift, and missense—in early-onset Alzheimer’s disease (EOAD, p value = 0.03, OR = 2.21 95% CI 1.05–4.82) and frontotemporal dementia (FTD, p = 0.006, OR = 2.59, 95% CI 1.28–5.49) patient cohorts. DPP6 is a type II transmembrane protein with a highly structured extracellular domain and is mainly expressed in brain, where it binds to the potassium channel Kv4.2 enhancing its expression, regulating its gating properties and controlling the dendritic excitability of hippocampal neurons. Using in vitro modeling, we showed that the missense variants found in patients destabilize DPP6 and reduce its membrane expression (p

Published
2019

22. Dementia, End of Life, and Euthanasia: A Survey Among Dementia Specialists Organized by the Belgian Dementia Council.

Author

UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (MGD) Service de neurologie, UCL - (SLuc) Service de neurologie, Picard, Gaëtane, Bier, Jean-Christophe, Capron, Isabelle, De Deyn, Peter Paul, Deryck, Olivier, Engelborghs, Sebastiaan, Hanseeuw, Bernard, Lemper, Jean-Claude, Mormont, Eric, Petrovic, Mirko, Salmon, Eric, Segers, Kurt, Sieben, Anne, Thiery, Evert, Ventura, Manfredi, Versijpt, Jan, Ivanoiu, Adrian, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (MGD) Service de neurologie, UCL - (SLuc) Service de neurologie, Picard, Gaëtane, Bier, Jean-Christophe, Capron, Isabelle, De Deyn, Peter Paul, Deryck, Olivier, Engelborghs, Sebastiaan, Hanseeuw, Bernard, Lemper, Jean-Claude, Mormont, Eric, Petrovic, Mirko, Salmon, Eric, Segers, Kurt, Sieben, Anne, Thiery, Evert, Ventura, Manfredi, Versijpt, Jan, and Ivanoiu, Adrian

Abstract

BACKGROUND: Palliative care and Advance Care Planning (ACP) are increasingly recommended for an optimal management of late-stage dementia. In Belgium, euthanasia has been decriminalized in 2002 for patients who are "mentally competent" (interpreted as non-demented). It has been suggested that advance directives for euthanasia (ADE) should be made possible for dementia patients. OBJECTIVE: This study presents the results of an internet survey among Belgian dementia specialists. METHODS: In 2013, the Belgian Dementia Council (BeDeCo) organized a debate on end of life decisions in dementia. Participants were medical doctors who are specialists in the dementia field. After the debate, an anonymous internet survey was organized. The participation rate was 55%. The sample was representative of the BeDeCo members. RESULTS: The results showed consensus in favor of palliative care and ACP, although ACP is not systematically addressed in practice. Few patients with dementia have requested euthanasia, but for those who did the participants had agreed to implement it for some patients. A majority of participants (94%) believe that most patients and their families are poorly informed about euthanasia. Although most participants (77%) said they approved the Law on euthanasia, 65% said they were against an extension of the Law to allow ADE for dementia. CONCLUSION: Palliative care and ACP are clearly accepted by professionals, although a gap between recommendation and practice remain. Euthanasia is a much more debated issue, even if a majority of professionals are, in principle, in favor of the current Law and seem to disapprove with a Law change allowing ADE for dementia. A better education for both health professionals and the lay public will be a key element in the future.

Published
2019

23. Dementia, End of Life, and Euthanasia: A Survey Among Dementia Specialists Organized by the Belgian Dementia Council

Author

Picard, Gaëtane, primary, Bier, Jean-Christophe, additional, Capron, Isabelle, additional, De Deyn, Peter Paul, additional, Deryck, Olivier, additional, Engelborghs, Sebastiaan, additional, Hanseeuw, Bernard, additional, Lemper, Jean-Claude, additional, Mormont, Eric, additional, Petrovic, Mirko, additional, Salmon, Eric, additional, Segers, Kurt, additional, Sieben, Anne, additional, Thiery, Evert, additional, Ventura, Manfredi, additional, Versijpt, Jan, additional, and Ivanoiu, Adrian, additional

Published
2019
Full Text
View/download PDF

24. A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER).

Author

UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (SLuc) Service de neurologie, UCL - (MGD) Service de neurologie, Niemantsverdriet, Ellis, Ribbens, Annemie, Bastin, Christine, Benoit, Florence, Bergmans, Bruno, Bier, Jean-Christophe, Bladt, Roxanne, Claes, Lene, De Deyn, Peter Paul, Deryck, Olivier, Hanseeuw, Bernard, Ivanoiu, Adrian, Lemper, Jean-Claude, Mormont, Eric, Picard, Gaëtane, Salmon, Eric, Segers, Kurt, Sieben, Anne, Smeets, Dirk, Struyfs, Hanne, Thiery, Evert, Tournoy, Jos, Triau, Eric, Vanbinst, Anne-Marie, Versijpt, Jan, Bjerke, Maria, Engelborghs, Sebastiaan, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (SLuc) Service de neurologie, UCL - (MGD) Service de neurologie, Niemantsverdriet, Ellis, Ribbens, Annemie, Bastin, Christine, Benoit, Florence, Bergmans, Bruno, Bier, Jean-Christophe, Bladt, Roxanne, Claes, Lene, De Deyn, Peter Paul, Deryck, Olivier, Hanseeuw, Bernard, Ivanoiu, Adrian, Lemper, Jean-Claude, Mormont, Eric, Picard, Gaëtane, Salmon, Eric, Segers, Kurt, Sieben, Anne, Smeets, Dirk, Struyfs, Hanne, Thiery, Evert, Tournoy, Jos, Triau, Eric, Vanbinst, Anne-Marie, Versijpt, Jan, Bjerke, Maria, and Engelborghs, Sebastiaan

Abstract

BACKGROUND: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). OBJECTIVE: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. METHODS: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n = 887) and follow-up (FU, n = 95) T1-weighted brain MRIs and time-linked neuropsychological data were available. RESULTS: The cohort consisted of cognitively healthy controls (HC, n = 93), subjective cognitive decline (n = 102), mild cognitive impairment (MCI, n = 379), and AD dementia (n = 313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n = 95) compared to HC (FU>24months, p = 0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment. CONCLUSION: WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials.

Published
2018

25. A Belgian consensus protocol for autologous hematopoietic stem cell transplantation in multiple sclerosis.

Author

UCL - (SLuc) Service de neurologie, UCL - (SLuc) Service d'hématologie, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Laureys, Guy, Willekens, Barbara, Vanopdenbosch, Ludo, Deryck, Olivier, Selleslag, Dominik, D'Haeseleer, Miguel, De Becker, Ann, Dubois, Bénédicte, Dierickx, Daan, Perrotta, Gaetano, De Wilde, Virginie, Van Pesch, Vincent, Straetmans, Nicole, Dive, Dominique, Beguin, Yves, Van Wijmeersch, Bart, Theunissen, Koen, Kerre, Tessa, Van de Velde, Ann, UCL - (SLuc) Service de neurologie, UCL - (SLuc) Service d'hématologie, UCL - SSS/IONS - Institute of NeuroScience, UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire, UCL - SSS/IREC/SLUC - Pôle St.-Luc, Laureys, Guy, Willekens, Barbara, Vanopdenbosch, Ludo, Deryck, Olivier, Selleslag, Dominik, D'Haeseleer, Miguel, De Becker, Ann, Dubois, Bénédicte, Dierickx, Daan, Perrotta, Gaetano, De Wilde, Virginie, Van Pesch, Vincent, Straetmans, Nicole, Dive, Dominique, Beguin, Yves, Van Wijmeersch, Bart, Theunissen, Koen, Kerre, Tessa, and Van de Velde, Ann

Abstract

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardized protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous hematopoietic stem cell transplantation in multiple sclerosis.

Published
2018

26. A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer's Disease (REMEMBER).

Author

Niemantsverdriet, Ellis, Ribbens, Annemie, Bastin, Christine, Benoit, Florence, Bergmans, Bruno, Bier, Jean Christophe, Bladt, Roxanne, Claes, Lene, De Deyn, Peter Paul, Deryck, Olivier, Hanseeuw, Bernard, Ivanoiu, Adrian, Lemper, Jean-Claude, Mormont, Eric, Picard, Gaëtane, Salmon, Eric, Segers, Kurt, Sieben, Anne, Smeets, Dirk, Struyfs, Hanne, Thiery, Evert, Tournoy, Jos, Triau, Eric, Vanbinst, Anne-Marie, Versijpt, Jan, Bjerke, Maria, Engelborghs, Sebastiaan, Niemantsverdriet, Ellis, Ribbens, Annemie, Bastin, Christine, Benoit, Florence, Bergmans, Bruno, Bier, Jean Christophe, Bladt, Roxanne, Claes, Lene, De Deyn, Peter Paul, Deryck, Olivier, Hanseeuw, Bernard, Ivanoiu, Adrian, Lemper, Jean-Claude, Mormont, Eric, Picard, Gaëtane, Salmon, Eric, Segers, Kurt, Sieben, Anne, Smeets, Dirk, Struyfs, Hanne, Thiery, Evert, Tournoy, Jos, Triau, Eric, Vanbinst, Anne-Marie, Versijpt, Jan, Bjerke, Maria, and Engelborghs, Sebastiaan

Abstract

Background: Magnetic resonance imaging (MRI) acquisition/processing techniques assess brain volumes to explore neurodegeneration in Alzheimer's disease (AD). Objective: We examined the clinical utility of MSmetrix and investigated if automated MRI volumes could discriminate between groups covering the AD continuum and could be used as a predictor for clinical progression. Methods: The Belgian Dementia Council initiated a retrospective, multi-center study and analyzed whole brain (WB), grey matter (GM), white matter (WM), cerebrospinal fluid (CSF), cortical GM (CGM) volumes, and WM hyperintensities (WMH) using MSmetrix in the AD continuum. Baseline (n=887) and follow-up (FU, n=95) T1-weighted brain MRIs and time-linked neuropsychological data were available. Results: The cohort consisted of cognitively healthy controls (HC, n=93), subjective cognitive decline (n=102), mild cognitive impairment (MCI, n=379), and AD dementia (n=313). Baseline WB and GM volumes could accurately discriminate between clinical diagnostic groups and were significantly decreased with increasing cognitive impairment. MCI patients had a significantly larger change in WB, GM, and CGM volumes based on two MRIs (n=95) compared to HC (FU>24months, p=0.020). Linear regression models showed that baseline atrophy of WB, GM, CGM, and increased CSF volumes predicted cognitive impairment. Conclusion: WB and GM volumes extracted by MSmetrix could be used to define the clinical spectrum of AD accurately and along with CGM, they are able to predict cognitive impairment based on (decline in) MMSE scores. Therefore, MSmetrix can support clinicians in their diagnostic decisions, is able to detect clinical disease progression, and is of help to stratify populations for clinical trials., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

27. A Belgian consensus protocol for autologous hematopoietic stem cell transplantation in multiple sclerosis

Author

Laureys, G., Willekens, Barbara, Vanopdenbosch, Ludo, Deryck, Olivier, Selleslag, Dominik, D’haeseleer, Miguel, De Becker, A., Dubois, Bénédicte, Dierickx, Daan, Perrotta, Gaetano, De Wilde, Virginie, Van Pesch, Vincent, Straetmans, Nicole, Dive, Dominique, Beguin, Yves, Van Wijmeersch, Bart, Theunissen, Koen, Kerre, Tessa, Van de Velde, Ann, Laureys, G., Willekens, Barbara, Vanopdenbosch, Ludo, Deryck, Olivier, Selleslag, Dominik, D’haeseleer, Miguel, De Becker, A., Dubois, Bénédicte, Dierickx, Daan, Perrotta, Gaetano, De Wilde, Virginie, Van Pesch, Vincent, Straetmans, Nicole, Dive, Dominique, Beguin, Yves, Van Wijmeersch, Bart, Theunissen, Koen, Kerre, Tessa, and Van de Velde, Ann

Abstract

Multiple sclerosis is considered to be an immune mediated inflammatory disorder of the central nervous system. It mainly affects young, socioeconomic active patients. Although our armamentarium for this disease has significantly evolved in recent years some patients remain refractory to conventional therapies. In these cases, autologous hematopoietic stem cell transplantation can be considered as a therapeutic option. Decreasing morbidity, mortality, and increasing patient awareness have led to rising inquiry by our patients about this treatment option. With the aim of a standardized protocol and data registration, a Belgian working party on stem cell therapy in multiple sclerosis was established. In this paper, we report the consensus protocol of this working party on autologous hematopoietic stem cell transplantation in multiple sclerosis., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2018

28. No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

Author

Baradaran-Heravi, Yalda, primary, Dillen, Lubina, additional, Nguyen, Hung Phuoc, additional, Van Mossevelde, Sara, additional, Baets, Jonathan, additional, De Jonghe, Peter, additional, Engelborghs, Sebastiaan, additional, De Deyn, Peter P., additional, Vandenbulcke, Mathieu, additional, Vandenberghe, Rik, additional, Van Damme, Philip, additional, Cras, Patrick, additional, Salmon, Eric, additional, Synofzik, Matthis, additional, Heutink, Peter, additional, Wilke, Carlo, additional, Simon-Sanchez, Javier, additional, Rojas-Garcia, Ricard, additional, Turon-Sans, Janina, additional, Lleó, Alberto, additional, Illán-Gala, Ignacio, additional, Clarimón, Jordi, additional, Borroni, Barbara, additional, Padovani, Alessandro, additional, Pastor, Pau, additional, Diez-Fairen, Monica, additional, Aguilar, Miquel, additional, Gelpi, Ellen, additional, Sanchez-Valle, Raquel, additional, Borrego-Ecija, Sergi, additional, Matej, Radoslav, additional, Parobkova, Eva, additional, Nacmias, Benedetta, additional, Sorbi, Sandro, additional, Bagnoli, Silvia, additional, de Mendonça, Alexandre, additional, Ferreira, Catarina, additional, Fraidakis, Matthew J., additional, Diehl-Schmid, Janine, additional, Alexopoulos, Panagiotis, additional, Almeida, Maria Rosário, additional, Santana, Isabel, additional, Van Broeckhoven, Christine, additional, van der Zee, Julie, additional, Goeman, Johan, additional, Nuytten, Dirk, additional, Sieben, Anne, additional, De Bleecker, Jan L., additional, Santens, Patrick, additional, Versijpt, Jan, additional, Michotte, Alex, additional, Ivanoiu, Adrian, additional, Deryck, Olivier, additional, Bergmans, Bruno, additional, Willems, Christiana, additional, De Klippel, Nina, additional, Peeters, Dirk, additional, Archettim, Silvana, additional, Bonomi, Elisa, additional, Piaceri, Irene, additional, Ferrari, Camilla, additional, Simões do Couto, Frederico, additional, Verdelho, Ana, additional, and Miltenberger-Miltényi, Gabriel, additional

Published
2018
Full Text
View/download PDF

29. Clinical variability and onset age modifiers in an extended Belgian GRN founder family

Author

Wauters, Eline, primary, Van Mossevelde, Sara, additional, Sleegers, Kristel, additional, van der Zee, Julie, additional, Engelborghs, Sebastiaan, additional, Sieben, Anne, additional, Vandenberghe, Rik, additional, Philtjens, Stéphanie, additional, Van den Broeck, Marleen, additional, Peeters, Karin, additional, Cuijt, Ivy, additional, De Coster, Wouter, additional, Van Langenhove, Tim, additional, Santens, Patrick, additional, Ivanoiu, Adrian, additional, Cras, Patrick, additional, De Bleecker, Jan L., additional, Versijpt, Jan, additional, Crols, Roeland, additional, De Klippel, Nina, additional, Martin, Jean-Jacques, additional, De Deyn, Peter P., additional, Cruts, Marc, additional, Van Broeckhoven, Christine, additional, Goeman, Johan, additional, Nuytten, Dirk, additional, Vandenbulcke, Mathieu, additional, Michotte, Alex, additional, Salmon, Eric, additional, Deryck, Olivier, additional, Bergmans, Bruno, additional, Willems, Christiana, additional, and Delbeck, Jean, additional

Published
2018
Full Text
View/download PDF

30. A Retrospective Belgian Multi-Center MRI Biomarker Study in Alzheimer’s Disease (REMEMBER)

Author

Niemantsverdriet, Ellis, primary, Ribbens, Annemie, additional, Bastin, Christine, additional, Benoit, Florence, additional, Bergmans, Bruno, additional, Bier, Jean-Christophe, additional, Bladt, Roxanne, additional, Claes, Lene, additional, De Deyn, Peter Paul, additional, Deryck, Olivier, additional, Hanseeuw, Bernard, additional, Ivanoiu, Adrian, additional, Lemper, Jean-Claude, additional, Mormont, Eric, additional, Picard, Gaëtane, additional, Salmon, Eric, additional, Segers, Kurt, additional, Sieben, Anne, additional, Smeets, Dirk, additional, Struyfs, Hanne, additional, Thiery, Evert, additional, Tournoy, Jos, additional, Triau, Eric, additional, Vanbinst, Anne-Marie, additional, Versijpt, Jan, additional, Bjerke, Maria, additional, and Engelborghs, Sebastiaan, additional

Published
2018
Full Text
View/download PDF

31. Common and rare TBK1 variants in early-onset Alzheimer disease in a European cohort

Author

Verheijen, Jan, primary, van der Zee, Julie, additional, Gijselinck, Ilse, additional, Van den Bossche, Tobi, additional, Dillen, Lubina, additional, Heeman, Bavo, additional, Gómez-Tortosa, Estrella, additional, Lladó, Albert, additional, Sanchez-Valle, Raquel, additional, Graff, Caroline, additional, Pastor, Pau, additional, Pastor, Maria A., additional, Benussi, Luisa, additional, Ghidoni, Roberta, additional, Binetti, Giuliano, additional, Clarimon, Jordi, additional, de Mendonça, Alexandre, additional, Gelpi, Ellen, additional, Tsolaki, Magda, additional, Diehl-Schmid, Janine, additional, Nacmias, Benedetta, additional, Almeida, Maria Rosário, additional, Borroni, Barbara, additional, Matej, Radoslav, additional, Ruiz, Agustín, additional, Engelborghs, Sebastiaan, additional, Vandenberghe, Rik, additional, De Deyn, Peter P., additional, Cruts, Marc, additional, Van Broeckhoven, Christine, additional, Sleegers, Kristel, additional, Goeman, Johan, additional, Nuytten, Dirk, additional, Vandenbulcke, Mathieu, additional, Santens, Patrick, additional, De Bleecker, Jan, additional, Sieben, Anne, additional, Dermaut, Bart, additional, Versijpt, Jan, additional, Michotte, Alex, additional, Deryck, Olivier, additional, Bergmans, Bruno, additional, Willems, Christiana, additional, Ivanoiu, Adrian, additional, Salmon, Eric, additional, Alexopoulos, Panagiotis, additional, Sorbi, Sandro, additional, Bessi, Valentina, additional, Bagnoli, Silvia, additional, Santana, Isabel, additional, Simões do Couto, Frederico, additional, Martins, Madalena, additional, Thonberg, Håkan, additional, Fratiglioni, Laura, additional, Padovani, Alessandro, additional, Rohan, Zdenek, additional, Razquin, Cristina, additional, Lorenzo, Elena, additional, Iglesias, Elena, additional, Seijo-Martínez, Manuel, additional, Rene, Ramon, additional, Gascon, Jordi, additional, Campdelacreu, Jaume, additional, Koutroumani, Maria, additional, Lleó, Alberto, additional, Fortea, Juan, additional, and Blesa, Rafael, additional

Published
2018
Full Text
View/download PDF

32. NEK1 genetic variability in a Belgian cohort of ALS and ALS-FTD patients

Author

Nguyen, Hung Phuoc, primary, Van Mossevelde, Sara, additional, Dillen, Lubina, additional, De Bleecker, Jan L., additional, Moisse, Matthieu, additional, Van Damme, Philip, additional, Van Broeckhoven, Christine, additional, van der Zee, Julie, additional, Engelborghs, Sebastiaan, additional, Crols, Roeland, additional, De Deyn, Peter P., additional, De Jonghe, Peter, additional, Baets, Jonathan, additional, Cras, Patrick, additional, Mercelis, Rudy, additional, Vandenberghe, Rik, additional, Sieben, Anne, additional, Santens, Patrick, additional, Ivanoiu, Adrian, additional, Deryck, Olivier, additional, Vanopdenbosch, Ludo, additional, and Delbeck, Jean, additional

Published
2018
Full Text
View/download PDF

33. TBK1Mutation Spectrum in an Extended European Patient Cohort with Frontotemporal Dementia and Amyotrophic Lateral Sclerosis

Author

UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, van der Zee, Julie, Gijselinck, Ilse, Van Mossevelde, Sara, Perrone, Federica, Dillen, Lubina, Heeman, Bavo, Bâumer, Veerle, Engelborghs, Sebastiaan, De Bleecker, Jan, Baets, Jonathan, Gelpi, Ellen, Rojas-García, Ricardo, Clarimón, Jordi, Lleó, Alberto, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Perneczky, Robert, Synofzik, Matthis, Just, Jennifer, Schöls, Ludger, Graff, Caroline, Thonberg, Hakan, Borroni, Barbara, Padovani, Alessandro, Jordanova, Albena, Sarafov, Stayko, Tournev, Ivailo, de Mendonça, Alexandre, Miltenberger-Miltényi, Gabriel, Simões do Couto, Frederico, Ramirez, Alfredo, Jessen, Frank, Heneka, Michael T., Gómez-Tortosa, Estrella, Danek, Adrian, Cras, Patrick, Vandenberghe, Rik, De Jonghe, Peter, De Deyn, Peter P., Sleegers, Kristel, Cruts, Marc, Van Broeckhoven, Christine, Goeman, Johan, Nuytten, Dirk, Smets, Katrien, Robberecht, Wim, Damme, Philip Van, Bleecker, Jan De, Santens, Patrick, Dermaut, Bart, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Delbeck, Jean, Bruyland, Marc, Willems, Christiana, Salmon, Eric, Pastor, Pau, Ortega-Cubero, Sara, Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, Hernàndez, Isabel, Boada, Mercè, Ruiz, Agustín, Sorbi, Sandro, Nacmias, Benedetta, Bagnoli, Silvia, Sanchez-Valle, Raquel, Llado, Albert, Santana, Isabel, Rosàrio Almeida, Maria, Frisoni, Giovanni B, Maetzler, Walter, Matej, Radoslav, Fraidakis, Matthew J., Kovacs, Gabor G., Fabrizi, Gian Maria, Testi, Silvia, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, van der Zee, Julie, Gijselinck, Ilse, Van Mossevelde, Sara, Perrone, Federica, Dillen, Lubina, Heeman, Bavo, Bâumer, Veerle, Engelborghs, Sebastiaan, De Bleecker, Jan, Baets, Jonathan, Gelpi, Ellen, Rojas-García, Ricardo, Clarimón, Jordi, Lleó, Alberto, Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Perneczky, Robert, Synofzik, Matthis, Just, Jennifer, Schöls, Ludger, Graff, Caroline, Thonberg, Hakan, Borroni, Barbara, Padovani, Alessandro, Jordanova, Albena, Sarafov, Stayko, Tournev, Ivailo, de Mendonça, Alexandre, Miltenberger-Miltényi, Gabriel, Simões do Couto, Frederico, Ramirez, Alfredo, Jessen, Frank, Heneka, Michael T., Gómez-Tortosa, Estrella, Danek, Adrian, Cras, Patrick, Vandenberghe, Rik, De Jonghe, Peter, De Deyn, Peter P., Sleegers, Kristel, Cruts, Marc, Van Broeckhoven, Christine, Goeman, Johan, Nuytten, Dirk, Smets, Katrien, Robberecht, Wim, Damme, Philip Van, Bleecker, Jan De, Santens, Patrick, Dermaut, Bart, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Delbeck, Jean, Bruyland, Marc, Willems, Christiana, Salmon, Eric, Pastor, Pau, Ortega-Cubero, Sara, Benussi, Luisa, Ghidoni, Roberta, Binetti, Giuliano, Hernàndez, Isabel, Boada, Mercè, Ruiz, Agustín, Sorbi, Sandro, Nacmias, Benedetta, Bagnoli, Silvia, Sanchez-Valle, Raquel, Llado, Albert, Santana, Isabel, Rosàrio Almeida, Maria, Frisoni, Giovanni B, Maetzler, Walter, Matej, Radoslav, Fraidakis, Matthew J., Kovacs, Gabor G., Fabrizi, Gian Maria, and Testi, Silvia

Abstract

We investigated the mutation spectrum of the TANK-Binding Kinase 1 (TBK1) gene and its associated phenotypic spectrum by exonic resequencing of TBK1 in a cohort of 2,538 patients with frontotemporal dementia (FTD), amyotrophic lateral sclerosis (ALS), or FTD plus ALS, ascertained within the European Early-Onset Dementia Consortium. We assessed pathogenicity of predicted protein-truncating mutations by measuring loss of RNA expression. Functional effect of in-frame amino acid deletions and missense mutations was further explored in vivo on protein level and in vitro by an NFκB-induced luciferase reporter assay and measuring phosphorylated TBK1. The protein-truncating mutations led to the loss of transcript through nonsense-mediated mRNA decay. For the in-frame amino acid deletions, we demonstrated loss of TBK1 or phosphorylated TBK1 protein. An important fraction of the missense mutations compromised NFκB activation indicating that at least some functions of TBK1 are lost. Although missense mutations were also present in controls, over three times more mutations affecting TBK1 functioning were found in the mutation fraction observed in patients only, suggesting high-risk alleles (P = 0.03). Total mutation frequency for confirmed TBK1 LoF mutations in the European cohort was 0.7%, with frequencies in the clinical subgroups of 0.4% in FTD, 1.3% in ALS, and 3.6% in FTD-ALS.

Published
2017

34. Clinical Evidence of Disease Anticipation in Families Segregating aC9orf72Repeat Expansion

Author

UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Van Mossevelde, Sara, van der Zee, Julie, Gijselinck, Ilse, Sleegers, Kristel, De Bleecker, Jan, Sieben, Anne, Vandenberghe, Rik, Van Langenhove, Tim, Baets, Jonathan, Deryck, Olivier, Santens, Patrick, Ivanoiu, Adrian, Willems, Christiana, Bäumer, Veerle, Van den Broeck, Marleen, Peeters, Karin, Mattheijssens, Maria, De Jonghe, Peter, Cras, Patrick, Martin, Jean-Jacques, Cruts, Marc, De Deyn, Peter P., Engelborghs, Sebastiaan, Van Broeckhoven, Christine, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Van Mossevelde, Sara, van der Zee, Julie, Gijselinck, Ilse, Sleegers, Kristel, De Bleecker, Jan, Sieben, Anne, Vandenberghe, Rik, Van Langenhove, Tim, Baets, Jonathan, Deryck, Olivier, Santens, Patrick, Ivanoiu, Adrian, Willems, Christiana, Bäumer, Veerle, Van den Broeck, Marleen, Peeters, Karin, Mattheijssens, Maria, De Jonghe, Peter, Cras, Patrick, Martin, Jean-Jacques, Cruts, Marc, De Deyn, Peter P., Engelborghs, Sebastiaan, and Van Broeckhoven, Christine

Abstract

IMPORTANCE: Patients carrying a C9orf72 repeat expansion leading to frontotemporal dementia and/or amyotrophic lateral sclerosis have highly variable ages at onset of disease, suggesting the presence of modifying factors. OBJECTIVE: To provide clinical-based evidence for disease anticipation in families carrying a C9orf72 repeat expansion by analyzing age at onset, disease duration, and age at death in successive generations. DESIGN, SETTING, AND PARTICIPANTS: This cohort study was performed from June 16, 2000, to June 1, 2016, in 36 extended Belgian families in which a C9orf72 repeat expansion was segregating. The generational effect on age at onset, disease duration, and age at death was estimated using a mixed effects Cox proportional hazards regression model, including random-effects terms for within-family correlation and kinship. Time until disease onset or last examination, time from disease onset until death or last examination, or age at death was collected for for 244 individuals (132 proven or obligate C9orf72 carriers), of whom 147 were clinically affected (89 proven or obligate C9orf72 carriers). MAIN OUTCOMES AND MEASURES: Generational effect on age at onset, disease duration, and age at death. RESULTS: Among the 111 individuals with age at onset available (66 men and 45 women; mean [SD] age, 57.2 [9.1] years), the mean (SD) age at onset per generation (from earliest-born to latest-born generation) was 62.5 (8.3), 57.1 (8.2), 54.6 (10.2), and 49.3 (7.5) years. Censored regression analysis on all affected and unaffected at-risk relatives confirmed a decrease in age at onset in successive generations (P < .001). No generational effect was observed for disease duration or age at death. CONCLUSIONS AND RELEVANCE: The clinical data provide supportive evidence for the occurrence of disease anticipation in families carrying a C9orf72 repeat expansion by means of a decrease in age at onset across successive generations. This finding may help clinicians decide

Published
2017

35. Investigating the role of ALS genes CHCHD10 and TUBA4A in Belgian FTD-ALS spectrum patients

Author

Perrone, Federica, primary, Nguyen, Hung Phuoc, additional, Van Mossevelde, Sara, additional, Moisse, Matthieu, additional, Sieben, Anne, additional, Santens, Patrick, additional, De Bleecker, Jan, additional, Vandenbulcke, Mathieu, additional, Engelborghs, Sebastiaan, additional, Baets, Jonathan, additional, Cras, Patrick, additional, Vandenberghe, Rik, additional, De Jonghe, Peter, additional, De Deyn, Peter P., additional, Martin, Jean-Jacques, additional, Van Damme, Philip, additional, Van Broeckhoven, Christine, additional, van der Zee, Julie, additional, Nuytten, Dirk, additional, Smets, Katrien, additional, Versijpt, Jan, additional, Michotte, Alex, additional, Ivanoiu, Adrian, additional, Deryck, Olivier, additional, Bergmans, Bruno, additional, Delbeck, Jean, additional, Bruyland, Marc, additional, Willems, Christiana, additional, and Salmon, Eric, additional

Published
2017
Full Text
View/download PDF

37. Clinical evidence for genetic anticipation in C9orf72 pedigrees

Author

Van Mossevelde Sara, Van Der Zee Julie, Gijselinck Ilse, Sieben Anne, De Bleecker Jan, Van Langenhove Tim, Ivanoiu Adrian, Deryck Olivier, Van Den Broeck Marleen, Mattheijssens Maria, Karin Peeters, De Jonghe Peter, De Deyn Peter, Cras Patrick, Martin Jean-Jacques, Cruts Marc, Engelborghs Sebastiaan, and Van Broeckhoven Christine

Subjects
General Neuroscience
Published
2015

38. The C9orf72 repeat size correlates with onset age of disease, DNA methylation and transcriptional downregulation of the promoter

Author

UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Gijselinck, Ilse, Van Mossevelde, Sara, van der Zee, Julie, Sieben, Anne, Engelborghs, Sebastiaan, De Bleecker, Jan, Ivanoiu, Adrian, Deryck, Olivier, Edbauer, Dieter, Zhang, Ming, Heeman, Bavo, Bäumer, Veerle, Van den Broeck, Marleen, Mattheijssens, Maria, Peeters, Karin, Rogaeva, Ekaterina, De Jonghe, Peter, Cras, Patrick, Martin, Jean-Jacques, de Deyn, Peter Paul, Cruts, Marc, Van Broeckhoven, Christine, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, Gijselinck, Ilse, Van Mossevelde, Sara, van der Zee, Julie, Sieben, Anne, Engelborghs, Sebastiaan, De Bleecker, Jan, Ivanoiu, Adrian, Deryck, Olivier, Edbauer, Dieter, Zhang, Ming, Heeman, Bavo, Bäumer, Veerle, Van den Broeck, Marleen, Mattheijssens, Maria, Peeters, Karin, Rogaeva, Ekaterina, De Jonghe, Peter, Cras, Patrick, Martin, Jean-Jacques, de Deyn, Peter Paul, Cruts, Marc, and Van Broeckhoven, Christine

Abstract

Pathological expansion of a G4C2 repeat, located in the 5' regulatory region of C9orf72, is the most common genetic cause of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). C9orf72 patients have highly variable onset ages suggesting the presence of modifying factors and/or anticipation. We studied 72 Belgian index patients with FTLD, FTLD–ALS or ALS and 61 relatives with a C9orf72 repeat expansion. We assessed the effect of G4C2 expansion size on onset age, the role of anticipation and the effect of repeat size on methylation and C9orf72 promoter activity. G4C2 expansion sizes varied in blood between 45 and over 2100 repeat units with short expansions (45–78 units) present in 5.6% of 72 index patients with an expansion. Short expansions co-segregated with disease in two families. The subject with a short expansion in blood but an indication of mosaicism in brain showed the same pathology as those with a long expansion. Further, we provided evidence for an association of G4C2 expansion size with onset age (P<0.05) most likely explained by an association of methylation state of the 5' flanking CpG island and expansion size in blood (P<0.0001) and brain (P<0.05). In several informative C9orf72 parent–child transmissions, we identified earlier onset ages, increasing expansion sizes and/or increasing methylation states (P=0.0034) of the 5' CpG island, reminiscent of disease anticipation. Also, intermediate repeats (7–24 units) showed a slightly higher methylation degree (P<0.0001) and a decrease of C9orf72 promoter activity (P<0.0001) compared with normal short repeats (2–6 units). Decrease of transcriptional activity was even more prominent in the presence of small deletions flanking G4C2 (P<0.0001). Here we showed that increased methylation of CpGs in the C9orf72 promoter may explain how an increasing G4C2 size lead to loss-of-function without excluding repeat length-dependent toxic gain-of-function. These data provide insights into di

Published
2016

39. Botulinum toxin infiltrations for chronic migraine are efficacious and safe: the Bruges experience

Author

Van Dycke Annelies, Bergmans Bruno, Verhoeven Kristof, Bruffaerts Rose, Verhalle Marie-damienne, and Deryck Olivier

Subjects
medicine.medical_specialty, business.industry, Botulinum toxin, Surgery, Behavioral Neuroscience, Psychiatry and Mental health, Neuropsychology and Physiological Psychology, Chronic Migraine, Neurology, Anesthesia, medicine, business, Biological Psychiatry, medicine.drug
Published
2014

40. Clinical Evidence for Disease Anticipation in Families Segregating a C9orf72 Repeat Expansion (S21.006)

Author

Van Mossevelde, Sara, primary, Van Der Zee, Julie, additional, Gijselinck, Ilse, additional, Sleegers, Kristel, additional, Van Langenhove, Tim, additional, Sieben, Anne, additional, De Bleecker, Jan, additional, Ivanoiu, Adrian, additional, Deryck, Olivier, additional, Santens, Patrick, additional, Baumer, Veerle, additional, Van Den Broeck, Marleen, additional, Mattheijssens, Maria, additional, Peeters, Karin, additional, De Jonghe, Peter, additional, De Deyn, Peter, additional, Cras, Patrick, additional, Vandenberghe, Rik, additional, Martin, Jean-Jacques, additional, Cruts, Marc, additional, Engelborghs, Sebastiaan, additional, and Van Broeckhoven, Christine, additional

Published
2016
Full Text
View/download PDF

41. Clinical utility and applicability of biomarker-based diagnostic criteria for Alzheimer's disease: a BeDeCo survey.

Author

UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, UCL - (MGD) Service de neurologie, Bier, Jean-Christophe, Verschraegen , Jurn, Vandenberghe , Rik, Guillaume , Bénédicte, Picard, Gaëtane, Otte , Georges, Mormont, Eric, Gilles, Christian, Segers, Kurt, Sieben, Anne, Thiery, Evert, Ventura, Manfredi, De Deyn, Peter, Deryck, Olivier, Versijpt, Jan, Salmon, Eric, Engelborghs, Sebastiaan, Ivanoiu, Adrian, UCL - SSS/IONS/NEUR - Clinical Neuroscience, UCL - (SLuc) Service de neurologie, UCL - (MGD) Service de neurologie, Bier, Jean-Christophe, Verschraegen , Jurn, Vandenberghe , Rik, Guillaume , Bénédicte, Picard, Gaëtane, Otte , Georges, Mormont, Eric, Gilles, Christian, Segers, Kurt, Sieben, Anne, Thiery, Evert, Ventura, Manfredi, De Deyn, Peter, Deryck, Olivier, Versijpt, Jan, Salmon, Eric, Engelborghs, Sebastiaan, and Ivanoiu, Adrian

Abstract

We conducted a survey regarding the medical care of patients with dementia in expert settings in Belgium. Open, unrestricted and motivated answers were centralized, blindly interpreted and structured into categories. The report of the results was then submitted to the participants in subsequent plenary meetings and through email. Fourteen experts responded to the questionnaire, confirming that recent propositions to modify Alzheimer's disease (AD) diagnostic criteria and options have stirred up debate among well-informed and dedicated experts in the field. The opinions were not unanimous and illustrate how difficult it is to find a standardized method of diagnosing this disease. The responses to the survey suggest that application of a step-by-step pragmatic method is used in practice. Only when the combination of clinical findings and classical structural neuro-imaging is insufficient for a diagnosis or suggests an atypical presentation, additional biomarkers are considered. Interestingly, few differences, if any, were observed between the use of biomarkers in MCI and in AD. In conclusion, the Belgian experts consulted in this survey were generally in agreement with the new diagnostic criteria for AD, although some concern was expressed about them being too "amyloidocentric". Although the clinical examination, including a full neuropsychological evaluation, is still considered as the basis for diagnosis, most experts also stated that they use biomarkers to help with diagnosis.

Published
2015

42. Clinical utility and applicability of biomarker-based diagnostic criteria for Alzheimer’s disease: a BeDeCo survey

Author

Bier, Jean Christophe, Verschraegen, Jurn, Vandenberghe, Rik, Guillaume, Bénédicte, Picard, Gaëtane, Otter, G., Mormont, Eric, Gilles, Christian, Segers, Kurt, Sieben, Anne, Thiery, Evert, Ventura, Manfredi, De Deyn, Peter Paul, Deryck, Olivier, Versijpt, Jan, Salmon, Eric, Engelborghs, Sebastiaan, Ivanoiu, Adrian, Bier, Jean Christophe, Verschraegen, Jurn, Vandenberghe, Rik, Guillaume, Bénédicte, Picard, Gaëtane, Otter, G., Mormont, Eric, Gilles, Christian, Segers, Kurt, Sieben, Anne, Thiery, Evert, Ventura, Manfredi, De Deyn, Peter Paul, Deryck, Olivier, Versijpt, Jan, Salmon, Eric, Engelborghs, Sebastiaan, and Ivanoiu, Adrian

Abstract

We conducted a survey regarding the medical care of patients with dementia in expert settings in Belgium. Open, unrestricted and motivated answers were centralized, blindly interpreted and structured into categories. The report of the results was then submitted to the participants in subsequent plenary meetings and through email. Fourteen experts responded to the questionnaire, confirming that recent propositions to modify Alzheimer’s disease (AD) diagnostic criteria and options have stirred up debate among well-informed and dedicated experts in the field. The opinions were not unanimous and illustrate how difficult it is to find a standardized method of diagnosing this disease. The responses to the survey suggest that application of a step-by-step pragmatic method is used in practice. Only when the combination of clinical findings and classical structural neuro-imaging is insufficient for a diagnosis or suggests an atypical presentation, additional biomarkers are considered. Interestingly, few differences, if any, were observed between the use of biomarkers in MCI and in AD. In conclusion, the Belgian experts consulted in this survey were generally in agreement with the new diagnostic criteria for AD, although some concern was expressed about them being too “amyloidocentric”. Although the clinical examination, including a full neuropsychological evaluation, is still considered as the basis for diagnosis, most experts also stated that they use biomarkers to help with diagnosis., SCOPUS: ar.j, info:eu-repo/semantics/published

Published
2015

43. No supportive evidence for TIA1 gene mutations in a European cohort of ALS-FTD spectrum patients

Author

Goeman, Johan, Nuytten, Dirk, Sieben, Anne, De Bleecker, Jan L., Santens, Patrick, Versijpt, Jan, Michotte, Alex, Ivanoiu, Adrian, Deryck, Olivier, Bergmans, Bruno, Willems, Christiana, De Klippel, Nina, Peeters, Dirk, Archettim, Silvana, Bonomi, Elisa, Piaceri, Irene, Ferrari, Camilla, Simões do Couto, Frederico, Verdelho, Ana, Miltenberger-Miltényi, Gabriel, Baradaran-Heravi, Yalda, Dillen, Lubina, Nguyen, Hung Phuoc, Van Mossevelde, Sara, Baets, Jonathan, De Jonghe, Peter, Engelborghs, Sebastiaan, De Deyn, Peter P., Vandenbulcke, Mathieu, Vandenberghe, Rik, Van Damme, Philip, Cras, Patrick, Salmon, Eric, Synofzik, Matthis, Heutink, Peter, Wilke, Carlo, Simon-Sanchez, Javier, Rojas-Garcia, Ricard, Turon-Sans, Janina, Lleó, Alberto, Illán-Gala, Ignacio, Clarimón, Jordi, Borroni, Barbara, Padovani, Alessandro, Pastor, Pau, Diez-Fairen, Monica, Aguilar, Miquel, Gelpi, Ellen, Sanchez-Valle, Raquel, Borrego-Ecija, Sergi, Matej, Radoslav, Parobkova, Eva, Nacmias, Benedetta, Sorbi, Sandro, Bagnoli, Silvia, de Mendonça, Alexandre, Ferreira, Catarina, Fraidakis, Matthew J., Diehl-Schmid, Janine, Alexopoulos, Panagiotis, Almeida, Maria Rosário, Santana, Isabel, Van Broeckhoven, Christine, and van der Zee, Julie

Published
2018
Full Text
View/download PDF

44. Clinical Evidence of Disease Anticipation in Families Segregating a C9orf72 Repeat Expansion.

Author

Van Mossevelde, Sara, van der Zee, Julie, Gijselinck, Ilse, Sleegers, Kristel, De Bleecker, Jan, Sieben, Anne, Vandenberghe, Rik, Van Langenhove, Tim, Baets, Jonathan, Deryck, Olivier, Santens, Patrick, Ivanoiu, Adrian, Willems, Christiana, Bäumer, Veerle, Van den Broeck, Marleen, Peeters, Karin, Mattheijssens, Maria, De Jonghe, Peter, Cras, Patrick, and Martin, Jean-Jacques

Published
2017
Full Text
View/download PDF

46. Clinical Evidence for Disease Anticipation in Families Segregating a C9orf72 Repeat Expansion

Author

Mossevelde, Sara, Zee, Julie, Gijselinck, Ilse, Sleegers, Kristel, Langenhove, Tim, Sieben, Anne, Bleecker, Jan, Ivanoiu, Adrian, Deryck, Olivier, Santens, Patrick, Baumer, Veerle, Den Broeck, Marleen, Matthegssens, Maria, Peeters, Karin, Jonghe, Peter, Deyn, Peter, Cras, Patrick, Vandenberghe, Rik, Martin, Jean-Jacques, Cruts, Marc, Engelborghs, Sebastiaan, Christine Van Broeckhoven, Clinical sciences, Neurology, and Pathologic Biochemistry and Physiology

Subjects
Medicine(all), C9orf72

47. Ofatumumab versus Teriflunomide in Multiple Sclerosis

Author

Hauser S. L., Bar-Or A., Cohen J. A., Comi G., Correale J., Coyle P. K., Cross A. H., de Seze J., Leppert D., Montalban X., Selmaj K., Wiendl H., Kerloeguen C., Willi R., Li B., Kakarieka A., Tomic D., Goodyear A., Pingili R., Haring D. A., Ramanathan K., Merschhemke M., Kappos L., Stephen L Hauser, Ludwig Kappos, Amit Bar-Or, Jeffrey A Cohen, Giancarlo Comi, Jorge Correale, Patricia K Coyle, Anne Cross, Jerome de Seze, Xavier Montalban, Krzysztof Selmaj, Heinz Wiendl, Stephen C Reingold, Garry R Cutter, Thomas Doerner, Hans-Peter Hartung, Per Soelberg Sørensen, Israel Steiner, Jerry S Wolinsky, Carlos Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana Liwacki, Jeannette Lechner-Scott, John Parratt, Suzanne Hodgkinson, Eva-Maria Maida, Fritz Leutmezer, Barbara Willekens, Bart Van Wijmeersch, Guy Laureys, Jo Caekebeke, Karine Geens, Ludo Vanopdenbosch, Olivier Deryck, Valerie Delvaux, Vincent Van Pesch, Ivan Milanov, Ivaylo Tarnev, Lyubomir Haralanov, Maria Manova Slavova, Penko Shotekov, Francois Emond, Francois Grandmaison, Francois Jacques, Liesly Lee, Marie Sarah Gagne Brosseau, Mark Freedman, Martin Cloutier, Robert Carruthers, Sarah Morrow, Yves Lapierre, Anton Vladic, Hana Bokun, Igor Antoncic, Marija Bosnjak Pasic, Mario Habek, Silva Butkovic Soldo, Vladimira Vuletic, Alena Martinkova, Eva Meluzinova, Ivana Stetkarova, Jan Mares, Jolana Markova, Marta Vachova, Martin Valis, Michaela Tyblova, Michal Dufek, Ondrej Skoda, Pavel Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina Svendsen, Mads Ravnborg, Peter Vestergaard Rasmussen, Katrin Gross-Paju, Sulev Haldre, Juha Pekka Eralinna, Marja-Liisa Sumelahti, Bruno Brochet, Celine Louapre, Christine Lebrun-Frenay, David Axel Laplaud, Gilles Edan, Giovanni Castelnovo, Marc Debouverie, Patrick Vermersch, Pierre Clavelou, Pierre Labauge, Achim Berthele, Aiden Haghikia, Anselm Kornhuber, Arnfin Bergmann, Benedikt Frank, Birte Elias-Hamp, Bjoern Tackenberg, Brigitte Wildemann, Erik Strauss, Eugen Schlegel, Florian Then Bergh, Gereon Nelles, Hayrettin Tumani, Karl-Otto Sigel, Martin Stangel, Matthias Boehringer, Olaf Martin Hoffmann, Patrick Oschmann, Reinhard Hohlfeld, Silke Walter, Sylvia Menck, Till Sprenger, Tjalf Ziemssen, Veit Ulrich Becker, Vera Straeten, Konstantinos Kilidireas, Konstantinos Voumvourakis, Nikolaos Fakas, Nikolaos Grigoriadis, Agnes Koves, Csilla Rozsa, Krisztina Kovacs, Laszlo Vecsei, Satori Maria, Zita Biro, Anshu Rohatgi, Dheeraj Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha Pandit, Meena Angamuthu Kanikannan, Pahari Ghosh, Rahul Chakor, Rahul Kulkarni, Roopkumar Gursahani, Sangeeta Ravat, Srinivasa Rangasetty, Suresh Kumar, Alla Shifrin, Arnon Karni, Radi Shahien, Ron Milo, Antonio Uccelli, Carlo Pozzilli, Francesco Sacca, Giacomo Lus, Girolama Alessandra Marfia, Laura Brambilla, Marco Salvetti, Massimo Filippi, Mauro Zaffaroni, Paolo Gallo, Silvia Rossi, Simona Bonavita, Valeria Studer, Andrejs Millers, Guntis Karelis, Jolanta Kalnina, Dalia Mickeviciene, Rasa Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs Wokke, Bob W Van Oosten, Peter Van Domburg, Raymond Hupperts, Rogier Q Hintzen, Astrid Edland, Cesar Castaneda, Julio Perez, Martin Gavidia, Andrzej Wiak, Bartosz Karaszewski, Elzbieta Jasinska, Halina Bartosik Psujek, Iwona Jastrzebska, Jaroslaw Slawek, Maciej Maciejowski, Miroslaw Dziki, Monika Adamczyk Sowa, Robert Bonek, Waldemar Fryze, Ana Martins Da Silva, Angela Timoteo, Antonio Vasco Salgado, Carlos Capela, Carlos Veira, Filipe Correia, Joao Cerqueira, Joao De Sa, Livia De Sousa, Raquel Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon Kurca, Georgi Krastev, Miroslav Brozman, Peter Koleda, Peter Turcani, Peter Valkovic, Viera Hancinova, Vladimir Donath, Chris Retief, Michael Isaacs, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik Piehl, Jan Lycke, Chiara Zecca, Tobias Derfuss, Thy-Sheng Lin, Somsak Tiamkao, Ayse Nur Yuceyar, Aysun Soysal, Belgin Petek Balci, Cavit Boz, Husnu Efendi, Murat Terzi, Serhan Sevim, Serkan Ozakbas, Andrew Gale, Ben Turner, David Barnes, David Paling, Eli Silber, James Overell, Matthew Craner, Aaron Carlson, Adam Wolff, Adaeze Onuoha, Adnan Subei, Ahmad Ata, Aimee Borazanci, Akram Dastagir, Alberto Vasquez, Alison Brooke Allen, Andrew P Keegan, Angel Carrasco, Angel R Chinea Martinez, Ann Bass, Annette Okai, April Erwin, Ariel Antezana-Antezana, Barbara Green, Bharathy E Sundaram, Bhupendra Khatri, Bhupesh Dihenia, Bogdan Gheorghiu, Brian Costell, Brian Steingo, Bruce L Hughes, Carrie M Hersh, Christopher Laganke, Christopher Luzzio, Corey Ford, Craig Edward Herrman, Craig Senzon, Cynthia Huffman, Daniel R Wynn, David D O Bear, David Lesch, David H Mattson, David Weisman, Deborah A Burke, Dennis W Dietrich, Deren Huang, Derrick Robertson, Djamchid Lotfi, Don Joseph Alfonso, Dusan Stefoski, Edward J Fox, Emily Pharr, Enrique Alvarez, Evanthia Bernitsas, Faria Amjad, Gabriel Pardo, Geoffrey Eubank, Gerald Mcintosh, Giles F Crowell, Hemanth Rao, J Michael Hemphill, Jack H Florin, Jacqueline Nicholas, James Napier, James Scott, Jason M Silversteen, Javier Vasallo, Jean-Raphael Schneider, Jeanette Wendt, Jeffrey Cohen, Jeffrey Gross, Jeffrey Groves, Jeffrey Kaplan, Jessica Stulc, Joanna A Cooper, John Foley, John Scagnelli, Jonathan C Calkwood, Jose Pizarro Otero, Jose Rafecas, Joshua Katz, Juliette S Saad, Katherine Standley, Keith Edwards, Kenneth Sharlin, Khurram Bashir, Kimberly Wagner, Kore Liow, Larry Lee Blankenship Jr, Laszlo Mate, Liliana Montoya, Lon D Lynn, Mark Agius, Mark Cascione, Mark Allan Goldstein, Mark Janicki, Martin R Bialow, Mary Denise Hughes, Matthew J Baker, Michelle Apperson, Michelle B Kuczma, M Mateo Paz Soldan, Mirela Cerghet, Nathaniel Robb Whaley, Paul K Winner, Pavle Repovic, Praful Kelkar, Romero Rekha Pillai, Ricardo Ayala, Richard Sater, Randall Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert Naismith, Ronald S Murray, Samuel Hunter, Sara Qureshi, Sharon Lynch, Sibyl Wray, Silvia R Delgado, Stacy Donlon, Stanley Cohan, Stanya Smith, Stuart James Shafer, Susan Azalone, Susan Hibbs, Tamara A Miller, Thomas Giancarlo, Troy Desai, Varun K Saxena, Virginia Simnad, William David Honeycutt, William Logan, William E McElveen, William Wagner, University of California [San Francisco] (UCSF), University of California, Perelman School of Medicine, University of Pennsylvania [Philadelphia], Cleveland Clinic, IRCCS Ospedale San Raffaele [Milan, Italy], Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia [Buenos Aires] (FLENI), FLENI, Stony Brook University [SUNY] (SBU), State University of New York (SUNY), Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), CIC Strasbourg (Centre d’Investigation Clinique Plurithématique (CIC - P) ), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Strasbourg (UNISTRA)-Hôpital de Hautepierre [Strasbourg]-Nouvel Hôpital Civil de Strasbourg, University Hospital Basel [Basel], Vall d'Hebron University Hospital [Barcelona], University of Warmia and Mazury [Olsztyn], University of Münster, Novartis Pharma S.A.S., Novartis Pharmaceuticals, University of Basel (Unibas), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université de Montpellier (UM), Willekens, Barbara, ASCLEPIOS I and ASCLEPIOS II Trial Groups, Hauser, S. L., Bar-Or, A., Cohen, J. A., Comi, G., Correale, J., Coyle, P. K., Cross, A. H., de Seze, J., Leppert, D., Montalban, X., Selmaj, K., Wiendl, H., Kerloeguen, C., Willi, R., Li, B., Kakarieka, A., Tomic, D., Goodyear, A., Pingili, R., Haring, D. A., Ramanathan, K., Merschhemke, M., Kappos, L., Asclepios, I and ASCLEPIOS II Trial Group, Filippi, M, L Hauser, Stephen, Kappos, Ludwig, Bar-Or, Amit, A Cohen, Jeffrey, Comi, Giancarlo, Correale, Jorge, K Coyle, Patricia, Cross, Anne, de Seze, Jerome, Montalban, Xavier, Selmaj, Krzysztof, Wiendl, Heinz, C Reingold, Stephen, R Cutter, Garry, Doerner, Thoma, Hartung, Hans-Peter, Soelberg Sørensen, Per, Steiner, Israel, S Wolinsky, Jerry, Ballario, Carlo, Calvo Vildoso, Christian, Gustavo Jose, Jorge, Haydee Deri, Norma, Liwacki, Susana, Lechner-Scott, Jeannette, Parratt, John, Hodgkinson, Suzanne, Maida, Eva-Maria, Leutmezer, Fritz, Van Wijmeersch, Bart, Laureys, Guy, Caekebeke, Jo, Geens, Karine, Vanopdenbosch, Ludo, Deryck, Olivier, Delvaux, Valerie, Van Pesch, Vincent, Milanov, Ivan, Tarnev, Ivaylo, Haralanov, Lyubomir, Manova Slavova, Maria, Shotekov, Penko, Emond, Francoi, Grandmaison, Francoi, Jacques, Francoi, Lee, Liesly, Sarah Gagne Brosseau, Marie, Freedman, Mark, Cloutier, Martin, Carruthers, Robert, Morrow, Sarah, Lapierre, Yve, Vladic, Anton, Bokun, Hana, Antoncic, Igor, Bosnjak Pasic, Marija, Habek, Mario, Butkovic Soldo, Silva, Vuletic, Vladimira, Martinkova, Alena, Meluzinova, Eva, Stetkarova, Ivana, Mares, Jan, Markova, Jolana, Vachova, Marta, Valis, Martin, Tyblova, Michaela, Dufek, Michal, Skoda, Ondrej, Hradilek, Pavel, Voldsgaard Jensen, Ana, Hvilsted Nielsen, Helle, Svendsen, Kristina, Ravnborg, Mad, Vestergaard Rasmussen, Peter, Gross-Paju, Katrin, Haldre, Sulev, Pekka Eralinna, Juha, Sumelahti, Marja-Liisa, Brochet, Bruno, Louapre, Celine, Lebrun-Frenay, Christine, Axel Laplaud, David, Edan, Gille, Castelnovo, Giovanni, Debouverie, Marc, Vermersch, Patrick, Clavelou, Pierre, Labauge, Pierre, Berthele, Achim, Haghikia, Aiden, Kornhuber, Anselm, Bergmann, Arnfin, Frank, Benedikt, Elias-Hamp, Birte, Tackenberg, Bjoern, Wildemann, Brigitte, Strauss, Erik, Schlegel, Eugen, Then Bergh, Florian, Nelles, Gereon, Tumani, Hayrettin, Sigel, Karl-Otto, Stangel, Martin, Boehringer, Matthia, Martin Hoffmann, Olaf, Oschmann, Patrick, Hohlfeld, Reinhard, Walter, Silke, Menck, Sylvia, Sprenger, Till, Ziemssen, Tjalf, Ulrich Becker, Veit, Straeten, Vera, Kilidireas, Konstantino, Voumvourakis, Konstantino, Fakas, Nikolao, Grigoriadis, Nikolao, Koves, Agne, Rozsa, Csilla, Kovacs, Krisztina, Vecsei, Laszlo, Maria, Satori, Biro, Zita, Rohatgi, Anshu, Khurana, Dheeraj, Durai Pandian, Jeyaraj, Dev Mukherji, Joy, Pandit, Lekha, Angamuthu Kanikannan, Meena, Ghosh, Pahari, Chakor, Rahul, Kulkarni, Rahul, Gursahani, Roopkumar, Ravat, Sangeeta, Rangasetty, Srinivasa, Kumar, Suresh, Shifrin, Alla, Karni, Arnon, Shahien, Radi, Milo, Ron, Uccelli, Antonio, Pozzilli, Carlo, Sacca, Francesco, Lus, Giacomo, Alessandra Marfia, Girolama, Brambilla, Laura, Salvetti, Marco, Filippi, Massimo, Zaffaroni, Mauro, Gallo, Paolo, Rossi, Silvia, Bonavita, Simona, Studer, Valeria, Millers, Andrej, Karelis, Gunti, Kalnina, Jolanta, Mickeviciene, Dalia, Kizlaitiene, Rasa, Carbajal Ramirez, Angelica, Jose Lopez Prieto, Juan, Wokke, Beatrij, W Van Oosten, Bob, Van Domburg, Peter, Hupperts, Raymond, Q Hintzen, Rogier, Edland, Astrid, Castaneda, Cesar, Perez, Julio, Gavidia, Martin, Wiak, Andrzej, Karaszewski, Bartosz, Jasinska, Elzbieta, Bartosik Psujek, Halina, Jastrzebska, Iwona, Slawek, Jaroslaw, Maciejowski, Maciej, Dziki, Miroslaw, Adamczyk Sowa, Monika, Bonek, Robert, Fryze, Waldemar, Martins Da Silva, Ana, Timoteo, Angela, Vasco Salgado, Antonio, Capela, Carlo, Veira, Carlo, Correia, Filipe, Cerqueira, Joao, De Sa, Joao, De Sousa, Livia, Gouveia, Raquel, Sergeevna Agafina, Alina, Naumovna Belova, Anna, Viktorovich Sazonov, Deni, Pokhabov, Dmitry, Igorevna Kairbekova, Ekaterina, Gennadievna Arefieva, Elena, Axatovich Khabirov, Farit, Vyacheslavovich Litvinenko, Igor, Stolyarov, Igor, Aleksandrovna Sokolova, Irina, Ivanovna Volkova, Larisa, Vafaevna Davydovskaya, Maria, Nikolaevna Zaharova, Maria, Alekseevna Malkova, Nadezhda, Agafonovna Totolyan, Natalia, Vasilievich Dorogov, Nikolay, Anatolievna Sivertseva, Stella, Kurca, Egon, Krastev, Georgi, Brozman, Miroslav, Koleda, Peter, Turcani, Peter, Valkovic, Peter, Hancinova, Viera, Donath, Vladimir, Retief, Chri, Isaacs, Michael, Saiz Hinarejos, Albert, Rodriguez Antigüedad, Alfredo, Casanova Estruch, Bonaventura, Oreja-Guevara, Celia, Reig Rosello, Gemma, Carlos Alvarez Cermeño, Jose, Martinez Rodriguez, Jose, Meca Lallana, Jose, Antonio Garcia Merino, Juan, Forero Diaz, Lucia, Costa Frossard Franca, Lucienne, Querol Gutierrez, Lui, Ramio Torrenta, Llui, Serrano Castro, Pedro, Arroyo Gonzalez, Rafael, Eichau Madueño, Sara, Martinez Yelamos, Sergio, Castillo Trivino, Tamara, Meca Lallana, Virgina, Montalban Gairin, Xaviere, Piehl, Fredrik, Lycke, Jan, Zecca, Chiara, Derfuss, Tobia, Lin, Thy-Sheng, Tiamkao, Somsak, Nur Yuceyar, Ayse, Soysal, Aysun, Petek Balci, Belgin, Boz, Cavit, Efendi, Husnu, Terzi, Murat, Sevim, Serhan, Ozakbas, Serkan, Gale, Andrew, Turner, Ben, Barnes, David, Paling, David, Silber, Eli, Overell, Jame, Craner, Matthew, Carlson, Aaron, Wolff, Adam, Onuoha, Adaeze, Subei, Adnan, Ata, Ahmad, Borazanci, Aimee, Dastagir, Akram, Vasquez, Alberto, Brooke Allen, Alison, P Keegan, Andrew, Carrasco, Angel, R Chinea Martinez, Angel, Bass, Ann, Okai, Annette, Erwin, April, Antezana-Antezana, Ariel, Green, Barbara, E Sundaram, Bharathy, Khatri, Bhupendra, Dihenia, Bhupesh, Gheorghiu, Bogdan, Costell, Brian, Steingo, Brian, L Hughes, Bruce, M Hersh, Carrie, Laganke, Christopher, Luzzio, Christopher, Ford, Corey, Edward Herrman, Craig, Senzon, Craig, Huffman, Cynthia, R Wynn, Daniel, O Bear, David D, Lesch, David, H Mattson, David, Weisman, David, A Burke, Deborah, W Dietrich, Denni, Huang, Deren, Robertson, Derrick, Lotfi, Djamchid, Joseph Alfonso, Don, Stefoski, Dusan, J Fox, Edward, Pharr, Emily, Alvarez, Enrique, Bernitsas, Evanthia, Amjad, Faria, Pardo, Gabriel, Eubank, Geoffrey, Mcintosh, Gerald, F Crowell, Gile, Rao, Hemanth, Michael Hemphill, J, H Florin, Jack, Nicholas, Jacqueline, Napier, Jame, Scott, Jame, M Silversteen, Jason, Vasallo, Javier, Schneider, Jean-Raphael, Wendt, Jeanette, Cohen, Jeffrey, Gross, Jeffrey, Groves, Jeffrey, Kaplan, Jeffrey, Stulc, Jessica, A Cooper, Joanna, Foley, John, Scagnelli, John, C Calkwood, Jonathan, Pizarro Otero, Jose, Rafecas, Jose, Katz, Joshua, S Saad, Juliette, Standley, Katherine, Edwards, Keith, Sharlin, Kenneth, Bashir, Khurram, Wagner, Kimberly, Liow, Kore, Lee Blankenship Jr, Larry, Mate, Laszlo, Montoya, Liliana, D Lynn, Lon, Agius, Mark, Cascione, Mark, Allan Goldstein, Mark, Janicki, Mark, R Bialow, Martin, Denise Hughes, Mary, J Baker, Matthew, Apperson, Michelle, B Kuczma, Michelle, Mateo Paz Soldan, M, Cerghet, Mirela, Robb Whaley, Nathaniel, K Winner, Paul, Repovic, Pavle, Kelkar, Praful, Rekha Pillai, Romero, Ayala, Ricardo, Sater, Richard, Trudell, Randall, Fairborn Armstrong, Robert, Thomas Nahouraii, Robert, Naismith, Robert, S Murray, Ronald, Hunter, Samuel, Qureshi, Sara, Lynch, Sharon, Wray, Sibyl, R Delgado, Silvia, Donlon, Stacy, Cohan, Stanley, Smith, Stanya, James Shafer, Stuart, Azalone, Susan, Hibbs, Susan, A Miller, Tamara, Giancarlo, Thoma, Desai, Troy, K Saxena, Varun, Simnad, Virginia, David Honeycutt, William, Logan, William, E McElveen, William, Wagner, William, Stephen, L Hauser, Ludwig, Kappo, Amit, Bar-Or, Jeffrey, A Cohen, Giancarlo, Comi, Jorge, Correale, Patricia, K Coyle, Anne, Cro, Jerome de Seze, Xavier, Montalban, Krzysztof, Selmaj, Heinz, Wiendl, Stephen, C Reingold, Garry, R Cutter, Thomas, Doerner, Hans-Peter, Hartung, Per Soelberg Sørensen, Israel, Steiner, Jerry, S Wolinsky, Carlos, Ballario, Christian Calvo Vildoso, Jorge Gustavo Jose, Norma Haydee Deri, Susana, Liwacki, Jeannette, Lechner-Scott, John, Parratt, Suzanne, Hodgkinson, Eva-Maria, Maida, Fritz, Leutmezer, Barbara, Willeken, Bart Van Wijmeersch, Guy, Laurey, Karine, Geen, Ludo, Vanopdenbosch, Olivier, Deryck, Valerie, Delvaux, Vincent Van Pesch, Ivan, Milanov, Ivaylo, Tarnev, Lyubomir, Haralanov, Maria Manova Slavova, Penko, Shotekov, Francois, Emond, Francois, Grandmaison, Francois, Jacque, Liesly, Lee, Marie Sarah Gagne Brosseau, Mark, Freedman, Martin, Cloutier, Robert, Carruther, Sarah, Morrow, Yves, Lapierre, Anton, Vladic, Hana, Bokun, Igor, Antoncic, Marija Bosnjak Pasic, Mario, Habek, Silva Butkovic Soldo, Vladimira, Vuletic, Alena, Martinkova, Eva, Meluzinova, Ivana, Stetkarova, Jan, Mare, Jolana, Markova, Marta, Vachova, Martin, Vali, Michaela, Tyblova, Michal, Dufek, Ondrej, Skoda, Pavel, Hradilek, Ana Voldsgaard Jensen, Helle Hvilsted Nielsen, Kristina, Svendsen, Mads, Ravnborg, Peter Vestergaard Rasmussen, Katrin, Gross-Paju, Sulev, Haldre, Juha Pekka Eralinna, Marja-Liisa, Sumelahti, Bruno, Brochet, Celine, Louapre, Christine, Lebrun-Frenay, David Axel Laplaud, Gilles, Edan, Giovanni, Castelnovo, Marc, Debouverie, Patrick, Vermersch, Pierre, Clavelou, Pierre, Labauge, Achim, Berthele, Aiden, Haghikia, Anselm, Kornhuber, Arnfin, Bergmann, Benedikt, Frank, Birte, Elias-Hamp, Bjoern, Tackenberg, Brigitte, Wildemann, Erik, Strau, Eugen, Schlegel, Florian Then Bergh, Gereon, Nelle, Hayrettin, Tumani, Karl-Otto, Sigel, Martin, Stangel, Matthias, Boehringer, Olaf Martin Hoffmann, Patrick, Oschmann, Reinhard, Hohlfeld, Silke, Walter, Sylvia, Menck, Till, Sprenger, Tjalf, Ziemssen, Veit Ulrich Becker, Vera, Straeten, Konstantinos, Kilidirea, Konstantinos, Voumvouraki, Nikolaos, Faka, Nikolaos, Grigoriadi, Agnes, Kove, Csilla, Rozsa, Krisztina, Kovac, Laszlo, Vecsei, Satori, Maria, Zita, Biro, Anshu, Rohatgi, Dheeraj, Khurana, Jeyaraj Durai Pandian, Joy Dev Mukherji, Lekha, Pandit, Meena Angamuthu Kanikannan, Pahari, Ghosh, Rahul, Chakor, Rahul, Kulkarni, Roopkumar, Gursahani, Sangeeta, Ravat, Srinivasa, Rangasetty, Suresh, Kumar, Alla, Shifrin, Arnon, Karni, Radi, Shahien, Ron, Milo, Antonio, Uccelli, Carlo, Pozzilli, Sacca', Francesco, Giacomo, Lu, Girolama Alessandra Marfia, Laura, Brambilla, Marco, Salvetti, Massimo, Filippi, Mauro, Zaffaroni, Paolo, Gallo, Silvia, Rossi, Simona, Bonavita, Valeria, Studer, Andrejs, Miller, Guntis, Kareli, Jolanta, Kalnina, Dalia, Mickeviciene, Rasa, Kizlaitiene, Angelica Carbajal Ramirez, Juan Jose Lopez Prieto, Beatrijs, Wokke, Bob, W Van Oosten, Peter Van Domburg, Raymond, Huppert, Rogier, Q Hintzen, Astrid, Edland, Cesar, Castaneda, Julio, Perez, Martin, Gavidia, Andrzej, Wiak, Bartosz, Karaszewski, Elzbieta, Jasinska, Halina Bartosik Psujek, Iwona, Jastrzebska, Jaroslaw, Slawek, Maciej, Maciejowski, Miroslaw, Dziki, Monika Adamczyk Sowa, Robert, Bonek, Waldemar, Fryze, Ana Martins Da Silva, Angela, Timoteo, Antonio Vasco Salgado, Carlos, Capela, Carlos, Veira, Filipe, Correia, Joao, Cerqueira, Joao De Sa, Livia De Sousa, Raquel, Gouveia, Alina Sergeevna Agafina, Anna Naumovna Belova, Denis Viktorovich Sazonov, Dmitry, Pokhabov, Ekaterina Igorevna Kairbekova, Elena Gennadievna Arefieva, Farit Axatovich Khabirov, Igor Vyacheslavovich Litvinenko, Igor, Stolyarov, Irina Aleksandrovna Sokolova, Larisa Ivanovna Volkova, Maria Vafaevna Davydovskaya, Maria Nikolaevna Zaharova, Nadezhda Alekseevna Malkova, Natalia Agafonovna Totolyan, Nikolay Vasilievich Dorogov, Stella Anatolievna Sivertseva, Egon, Kurca, Georgi, Krastev, Miroslav, Brozman, Peter, Koleda, Peter, Turcani, Peter, Valkovic, Viera, Hancinova, Vladimir, Donath, Chris, Retief, Michael, Isaac, Albert Saiz Hinarejos, Alfredo Rodriguez Antigüedad, Bonaventura Casanova Estruch, Celia, Oreja-Guevara, Gemma Reig Rosello, Jose Carlos Alvarez Cermeño, Jose Martinez Rodriguez, Jose Meca Lallana, Juan Antonio Garcia Merino, Lucia Forero Diaz, Lucienne Costa Frossard Franca, Luis Querol Gutierrez, Lluis Ramio Torrenta, Pedro Serrano Castro, Rafael Arroyo Gonzalez, Sara Eichau Madueño, Sergio Martinez Yelamos, Tamara Castillo Trivino, Virgina Meca Lallana, Xaviere Montalban Gairin, Fredrik, Piehl, Jan, Lycke, Chiara, Zecca, Tobias, Derfu, Thy-Sheng, Lin, Somsak, Tiamkao, Ayse Nur Yuceyar, Aysun, Soysal, Belgin Petek Balci, Cavit, Boz, Husnu, Efendi, Murat, Terzi, Serhan, Sevim, Serkan, Ozakba, Andrew, Gale, Ben, Turner, David, Barne, David, Paling, Eli, Silber, James, Overell, Matthew, Craner, Aaron, Carlson, Adam, Wolff, Adaeze, Onuoha, Adnan, Subei, Ahmad, Ata, Aimee, Borazanci, Akram, Dastagir, Alberto, Vasquez, Alison Brooke Allen, Andrew, P Keegan, Angel, Carrasco, Angel, R Chinea Martinez, Ann, Ba, Annette, Okai, April, Erwin, Ariel, Antezana-Antezana, Barbara, Green, Bharathy, E Sundaram, Bhupendra, Khatri, Bhupesh, Dihenia, Bogdan, Gheorghiu, Brian, Costell, Brian, Steingo, Bruce, L Hughe, Carrie, M Hersh, Christopher, Laganke, Christopher, Luzzio, Corey, Ford, Craig Edward Herrman, Craig, Senzon, Cynthia, Huffman, Daniel, R Wynn, David D, O Bear, David, Lesch, David, H Mattson, David, Weisman, Deborah, A Burke, Dennis, W Dietrich, Deren, Huang, Derrick, Robertson, Djamchid, Lotfi, Don Joseph Alfonso, Dusan, Stefoski, Edward, J Fox, Emily, Pharr, Enrique, Alvarez, Evanthia, Bernitsa, Faria, Amjad, Gabriel, Pardo, Geoffrey, Eubank, Gerald, Mcintosh, Giles, F Crowell, Hemanth, Rao, J Michael Hemphill, Jack, H Florin, Jacqueline, Nichola, James, Napier, James, Scott, Jason, M Silversteen, Javier, Vasallo, Jean-Raphael, Schneider, Jeanette, Wendt, Jeffrey, Cohen, Jeffrey, Gro, Jeffrey, Grove, Jeffrey, Kaplan, Jessica, Stulc, Joanna, A Cooper, John, Foley, John, Scagnelli, Jonathan, C Calkwood, Jose Pizarro Otero, Jose, Rafeca, Joshua, Katz, Juliette, S Saad, Katherine, Standley, Keith, Edward, Kenneth, Sharlin, Khurram, Bashir, Kimberly, Wagner, Kore, Liow, Larry Lee Blankenship Jr, Laszlo, Mate, Liliana, Montoya, Lon, D Lynn, Mark, Agiu, Mark, Cascione, Mark Allan Goldstein, Mark, Janicki, Martin, R Bialow, Mary Denise Hughes, Matthew, J Baker, Michelle, Apperson, Michelle, B Kuczma, M Mateo Paz Soldan, Mirela, Cerghet, Nathaniel Robb Whaley, Paul, K Winner, Pavle, Repovic, Praful, Kelkar, Romero Rekha Pillai, Ricardo, Ayala, Richard, Sater, Randall, Trudell, Robert Fairborn Armstrong, Robert Thomas Nahouraii, Robert, Naismith, Ronald, S Murray, Samuel, Hunter, Sara, Qureshi, Sharon, Lynch, Sibyl, Wray, Silvia, R Delgado, Stacy, Donlon, Stanley, Cohan, Stanya, Smith, Stuart James Shafer, Susan, Azalone, Susan, Hibb, Tamara, A Miller, Thomas, Giancarlo, Troy, Desai, Varun, K Saxena, Virginia, Simnad, William David Honeycutt, William, Logan, William, E McElveen, William, Wagner, University of California [San Francisco] (UC San Francisco), University of California (UC), University of Pennsylvania, Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Nouvel Hôpital Civil de Strasbourg-Hôpital de Hautepierre [Strasbourg], Westfälische Wilhelms-Universität Münster = University of Münster (WWU), Herrada, Anthony, and UCL - SSS/IONS/CEMO - Pôle Cellulaire et moléculaire

Subjects
Male, MESH: Multiple Sclerosis, Relapsing-Remitting, T-Lymphocytes, Hydroxybutyrates, Kaplan-Meier Estimate, 030204 cardiovascular system & hematology, Pharmacology, Relapsing-Remitting, MESH: Magnetic Resonance Imaging, chemistry.chemical_compound, 0302 clinical medicine, Teriflunomide, Monoclonal, MESH: Double-Blind Method, 030212 general & internal medicine, Humanized, MESH: Toluidines, B-Lymphocytes, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, biology, Subcutaneous, B-Lymphocyte, Brain, General Medicine, Magnetic Resonance Imaging, MESH: Crotonates, Crotonates, Pyrimidine metabolism, Disease Progression, Female, MESH: Disease Progression, Antibody, Human, Adult, Multiple Sclerosis, Toluidines, medicine.drug_class, Injections, Subcutaneous, Injections, Subcutaneou, Monoclonal antibody, Ofatumumab, Settore MED/26, Antibodies, Monoclonal, Humanized, Crotonate, Antibodies, Injections, 03 medical and health sciences, MESH: Brain, Multiple Sclerosis, Relapsing-Remitting, Double-Blind Method, MESH: B-Lymphocytes, Nitriles, medicine, Humans, MESH: Kaplan-Meier Estimate, MESH: Humans, business.industry, Multiple sclerosis, MESH: Injections, Subcutaneous, MESH: Adult, medicine.disease, MESH: Male, MESH: T-Lymphocytes, T-Lymphocyte, Multicenter study, chemistry, MESH: Antibodies, Monoclonal, Humanized, biology.protein, Human medicine, business, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Background: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known.Methods: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume.Results: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P

Published
2020

48. Patients carrying the mutation p.R406W in MAPT present with non-conforming phenotypic spectrum.

Author

Gossye H, Van Mossevelde S, Sieben A, Bjerke M, Hendrickx Van de Craen E, van der Zee J, De Deyn PP, De Bleecker J, Versijpt J, van den Ende J, Deryck O, Bourgeois P, Bier JC, Goethals M, Vandenberghe R, Engelborghs S, and Van Broeckhoven C

Subjects
Humans, tau Proteins genetics, Mutation genetics, Phenotype, Biomarkers, Alzheimer Disease diagnostic imaging, Alzheimer Disease genetics, Frontotemporal Dementia diagnostic imaging, Frontotemporal Dementia genetics, Frontotemporal Dementia pathology, Frontotemporal Lobar Degeneration pathology, Pick Disease of the Brain
Abstract

The missense mutation p.R406W in microtubule-associated protein tau leads to frontotemporal lobar degeneration with an amnestic, Alzheimer's disease-like phenotype with an autosomal dominant pattern of inheritance. In 2003, we described the pedigree of a Belgian family, labelled ADG, with 28 p.R406W patients. Over 18 years follow-up, we extended the family with 10 p.R406W carriers and provided an in-depth clinical description of the patients. Additionally, genetic screening was used to identify p.R406W carriers in Belgian cohorts of frontotemporal dementia and Alzheimer's disease patients and to calculate p.R406W frequency. In the frontotemporal dementia cohort, we found four p.R406W carriers (n = 647, 0.62%) and three in the Alzheimer's disease cohort (n = 1134, 0.26%). Haplotype sharing analysis showed evidence of a shared haplotype suggesting that they are descendants of a common ancestor. Of the p.R406W patients, we describe characteristics of neuropsychological, imaging and fluid biomarkers as well as neuropathologic examination. Intriguingly, the phenotypic spectrum among the p.R406W patients ranged from typical behavioural variant frontotemporal dementia to clinical Alzheimer's disease, based on CSF biomarker analysis and amyloid PET scan. Heterogeneous overlap syndromes existed in between, with highly common neuropsychiatric symptoms like disinhibition and aggressiveness, which occurred in 100% of frontotemporal dementia and 58% of clinical Alzheimer's disease patients. This was also the case for memory problems, 89% in frontotemporal dementia and 100% in clinical Alzheimer's disease patients. Median age at death was significantly lower in patients with frontotemporal dementia (68 years) compared to clinical Alzheimer's disease patients (79 years), although the sizes of the sub-cohorts are limited and do not allow prognostic predictions. Post-mortem brain analysis of one p.R406W patient with behavioural variant frontotemporal dementia revealed frontotemporal lobar degeneration with tau pathology. Notably, neuropathological investigation showed only 3R tau isoforms in the absence of 4R tau reactivity, an unusual finding in microtubule-associated protein tau-related frontotemporal lobar degeneration. No traces of amyloid pathology were present. Prevalence of the p.R406W mutation was relatively high in both frontotemporal dementia and Alzheimer's disease Belgian patient cohorts. These findings grant new insights into genotype-phenotype correlations of p.R406W carriers. They may help in further unravelling of the pathophysiology of this tauopathy and in facilitating the identification of patients with p.R406W-related frontotemporal lobar degeneration, both in clinical diagnostic and research settings., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results