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Sub theme 2.6
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Goals of research: general outline |
Research of the Dept. of Neurology in neuromuscular and neuroinflammatory disorders is focused a. on Guillain-Barré syndrome (GBS) an immune-mediated disorder of the peripheral nervous system; and b. on MS, an inflammatory disorder of the central nervous system (CNS). Both disorders are considered to be diseases in which infections, genetic background and - at least in GBS - molecular mimicry plays an important role. Our research is typically translational in which large patient cohorts have been established and are followed for a long period of time. In GBS, these cohorts are mainly derived form the RCT’s that we have executed over the years. In MS, we have established the ErasMS center. This forms the basis of our immunologic and genetic studies that are done on close collaboration with several groups from ErasmusMC, especially from the Departments of Immunology, Genetic-epidemiology, Microbiology and Virology and with leading groups around the world. GBS GBS is a post-infectious immune-mediated polyneuropathy leading to a severe paresis within days to weeks. Recovery generally takes a long time and is often far from complete. Our patient cohorts are primarily based upon several randomized controlled clinical trials that we have conducted over the years. Our trials have been pivotal in showing that IVIg is effective for GBS, and for its chronic variety CIDP. IVIg currently is (world-wide) the first treatment choice for GBS. Using the data of the different studies, we have been able to establish one of the world’s largest bio-bank (serum DNA, skin biopsies and PBMC) with detailed long-term clinical information. Extensive studies on clinical associations with anti-ganglioside antibodies and DNA variants (SNP) have been performed, mainly in close collaboration with the Department of Immunology (Prof dr J. Laman). Using our clinical databank, we successfully started studies on prognostic modeling (Prof dr. E.W. Steyerberg) MS MS (multiple sclerosis) is an inflammatory disorder of the central nervous system (CNS) leading to neurodegeneration. It is the number one cause of neurological disability amongst young adults, who carry this ailment with them throughout their further life. MS can also have its onset during childhood, in approx. 3-5% of the cases. The cause of MS lies in a complex and poorly understood interplay of genetic and environmental factors (sunlight exposure, dietary conditions and infections). Next to the practical burden of neurological dysfunction, there is also the problem of uncertainty. Special uncertainty is felt after a first attack of what is suspected to evolve into MS at a later stage. There is an urgent need for better insight in the prognosis of an individual patient, in initiation of the proper therapy and, related to this, in the cause of MS. Our research focuses on the identification of biological factors that determine cause and course of the disease. The translational programme will also facilitate the identification of novel biomarkers. Goals One of the leading premises of ErasMS and GBS research is that excellent translational research can only be achieved in a centre with highly committed care facilities, and vice versa that patient care strongly benefits from a critical, academic research environment. Hence, our overall goal is to implement a high level translational approach on biological determinants of these diseases to further dissect cause and course. More specifically, we aim to directly link the top expertise of local departments (Neurology, Immunology, Genetics, Microbiology, Virology, Biomics facilities) to patient-oriented problems. Importantly, we desire to have an infrastructure for flexible research, directly applicable in case of novel insights into the field. Our overall aims within the frame of GBS and MS are: GBS
MS
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Scientific achievements |
GBS
MS
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Future plans: special goals and approach |
GBS
MS
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Most recent publications |
1. Van Koningsveld R, Schmitz PIM, van der Meché GFA, Visser LH, Meulstee J, van Doorn PA for the Dutch GBS Studygroup. Effect of methylprednisolone when added to standard treatment with intravenous immunoglobulin for Guillain-Barré syndrome. Lancet 2004;363:192-96. 2. Van Doorn PA, Ruts L, Jacobs BC. Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome. Lancet Neurology 2008;7:939-50. 3. Van Koningsveld R, Steyerberg EW, Hughes RA, Swan AV, van Doorn PA, Jacobs BC. A clinical prognostic scoring system for Guillain-Barré syndrome. Lancet Neurol 2007;6:589-94. 4. Halstead SK, Zitman FM, Humphreys PD, Greenshields K, Verschuuren JJ, Jacobs BC, Rother RP, Plomp JJ, Willison HJ. Eculizumab prevents anti-ganglioside antibody-mediated neuropathy in a murine model. Brain 2008;131:1197-1208 5. Geleijns K, Roos A, Houwing-Duistermaat JJ, Van Rijs W, Tio-Gillen AP, Laman JD, van Doorn PA, Jacobs BC. Mannose-binding lection contributes to the severity of Guillain-Barré syndrome. J Immunol 2006;177:4211-7. 6. Y Aulchenko , I Hoppenbrouwers, S Ramagopalan, L Broer, N Jafari , J Hillert , J Link , W Lundström , E Greiner , A Sadovnick , D Goossens , C van Broeckhoven , J Del-Favero, GC Ebers, B Oostra, C van Duijn, RQ Hintzen. Genetic variation in the KIF1B locus influences susceptibility to multiple sclerosis. Nat Genet. 2008 Dec;40(12):1402-3. 7. GM Verjans, RQ Hintzen, JM van Dun, A Poot, JC Milikan, JD Laman, AW Langerak, PR Kinchington, AD Osterhaus. Selective retention of herpes simplex virus-specific T cells in latently infected human trigeminal ganglia. Proc Natl Acad Sci U S A.2007;104:3496-501 8. RF Neuteboom, M Boon, CE Catsman Berrevoets, JS Vles, RH Gooskens, H Stroink, RJ Vermeulen, JJ Rotteveel, IA Ketelslegers, E Peeters, BT Poll-The, JF De Rijk-Van Andel, A Verrips, RQ Hintzen. Prognostic factors after a first attack of inflammatory CNS demyelination in children. Neurology 2008:71:967-73 9. T Vandercamme, RQ Hintzen, JH de Boer, A van der Lely. Herpetic Encephalitis is a risk factor for Acute Retinal Necrosis. Neurology 2008;71:1268-1274 10. MP Stoop, LJ Dekker, MK Titulaer, PC Burgers, PA Sillevis Smitt, TM Luider, RQ Hintzen. Multiple sclerosis-related proteins identified in cerebrospinal fluid by advanced mass spectrometry. Proteomics. 2008;8:1576-85 |