The mechanisms involved in the autoimmune hypothesis of narcolepsy are investigated in this thesis. The role of HLA, auto- and cross-reactive T cells is explored and immune cell populations of... Show moreThe mechanisms involved in the autoimmune hypothesis of narcolepsy are investigated in this thesis. The role of HLA, auto- and cross-reactive T cells is explored and immune cell populations of interest are identified by a new technique, called mass cytometry. The second part of the thesis assesses unexplored clinical features of narcolepsy, such as weight gain and sleep state misperception. Show less
Fatigue is usually defined as a subjective perception of lacking energy, mentally or physically, with a difficulty sustaining voluntary activities. It is a common symptom of many diseases and most... Show moreFatigue is usually defined as a subjective perception of lacking energy, mentally or physically, with a difficulty sustaining voluntary activities. It is a common symptom of many diseases and most likely has a multifactorial cause. In myasthenia gravis (MG), fatigue has a high prevalence and is correlated with female sex and disease severity. However, no large scale studies have been performed. Therefore, we aimed to evaluate fatigue in the Dutch participants (n = 420) of the Dutch-Belgian Myasthenia Patient Registry using an online survey. Additional information was obtained on mood, sleep, coping, quality of life, disease severity, physical activities and medication. Severe fatigue was present in 62% with a mean score of 37.1 +/- 13.2 points. Fatigue severity and prevalence increased significantly with disease severity. A positive correlation was found for female gender, BMI, disease severity and depressive symptoms. A negative correlation was found for strenuous physical activities and older age. The strong association with disease severity suggests that fatigue should be recognized as an element of the symptomatology of MG. The observed association between strenuous activity and fatigue and differences in coping style between fatigued and non-fatigued patients warrant future clinical trials on exercise and cognitive behavioral therapy. (C) 2021 The Authors. Published by Elsevier B.V. Show less
Narcolepsy is a disorder of the regulation of sleep and wakefulness, with as its major features excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and... Show moreNarcolepsy is a disorder of the regulation of sleep and wakefulness, with as its major features excessive daytime sleepiness (EDS), cataplexy, hypnagogic hallucinations, sleep paralysis and disturbed nocturnal sleep. The first part of this thesis concernes an overview of the pathophysiology, symptoms and treatment of narcolepsy type 1. The second part elaborates some pathophysiological aspects, focussing on the autoimmune hypothesis of narcolepsy. The third part focuses on alterations of temperature regulation and on measuring treatment effects of symptomatic treatment on sustained attention, i.e. vigilance. Show less
Heide, A. van der; Hegeman-Kleinn, I.M.; Peeters, E.; Lammers, G.J.; Fronczek, R. 2015
Sporadische inclusion body myositis (IBM) is een van de meest voor voorkomende verworven spierziekte die ontstaat na het 50e levensjaar. In dit proefschrift worden de klinische aspecten van... Show moreSporadische inclusion body myositis (IBM) is een van de meest voor voorkomende verworven spierziekte die ontstaat na het 50e levensjaar. In dit proefschrift worden de klinische aspecten van sporadische IBM beschreven. Uit de studie met betrekking tot het natuurlijk beloop blijkt dat de ziekte niet levensverkortend is, maar dat de doodsoorzaken bij sporadische IBM wel verschillen ten opzichte van een voor de leeftijd gecorrigeerde populatie. De aard en frequentie van slikstoornissen worden beschreven, alsmede de potentiele betrokkenheid van het hart. Door middel van MRI's van skeletspieren is een voor sporadische IBM specifiek patroon van afwijkingen beschreven. Ten slotte is aangetoond dat TREX1 mutaties geen rol spelen in het ontstaan van de ziekte. Show less
Rheumatoid Arthritis (RA) is a chronic autoimmune disease, affecting a ~1% of the population worldwide. Although its causes are largely unknown, a considerable heritable component approximating 50... Show moreRheumatoid Arthritis (RA) is a chronic autoimmune disease, affecting a ~1% of the population worldwide. Although its causes are largely unknown, a considerable heritable component approximating 50-60% has been described. The most prominent genetic association in RA is confined to the human leukocyte antigen (HLA) locus which has been known for ~30 years. The identification of RA-associated genes outside of the HLA region, however, had been a challenge. A few years ago, one such gene, protein tyrosine phosphatase, non-receptor type 22 (lymphoid), was identified in a large genetic-association study utilizing putative functional SNPs. The aim of this thesis was to take a candidate gene approach to identify risk factors involved in rheumatoid arthritis. It is divided into three parts in which part one is dedicated towards the identification of a novel risk factor for RA and autoimmunity. This region of the genome encompasses genes highly involved in the immune system, namely Tumour Necrosis Factor Receptor associated factor 1/Complement component 5 on chromosome 9q33. In the second part, we have investigated the role of an immunoregulatory cytokine interleukin 10 located on chromosome 1q32 and in part three we have investigated the role of additional genetic risk factors in RA. Show less
