BackgroundAs Huntington's disease (HD) is a progressive disease for which there is no cure yet, patients in the advanced stage of HD may benefit from palliative care.ObjectiveTo review the... Show moreBackgroundAs Huntington's disease (HD) is a progressive disease for which there is no cure yet, patients in the advanced stage of HD may benefit from palliative care.ObjectiveTo review the literature focusing on palliative care in advanced stage HD, and the level of evidence.MethodsPublications between 1993 and October 29th, 2021 from 8 databases (Embase, Web of Science, Cochrane, Emcare, PsycINFO, Academic Search Premier, PMC PubMed Central and Pubmed) were included. The literature was deductively classified based on topics that are part of the definition of palliative care, or as care-related topics that emerged from the literature. Levels of evidence I (high) - V (low) were determined as defined by the Joanna Briggs Institute.ResultsOur search resulted in 333 articles, 38 of which were included. The literature covered four domains of palliative care: physical care, psychological care, spiritual care, and social care. Four other topics in the literature were: advance care planning, end-of-life needs assessments, pediatric HD care, and need for health care services. Most literature was underpinned by a low level of evidence, except for the topics on social care (Level III-V), advance care planning (Level II-V) and end-of-life needs assessments (Level II-III).ConclusionsTo deliver adequate palliative care in advanced HD, both general and HD-specific symptoms and problems need to be addressed. As the level of evidence in existing literature is low, further research is essential to improve palliative care and to meet patient's wishes and needs. Show less
Feleus, S.; Schaijk, M. van; Roos, R.A.C.; Bot, S.T. de 2022
Huntington's Disease (HD) is a rare, neurodegenerative disorder characterized by chorea, cognitive decline, and behavioral changes. Despite wide clinical use since the mid-1980s, tiapride was... Show moreHuntington's Disease (HD) is a rare, neurodegenerative disorder characterized by chorea, cognitive decline, and behavioral changes. Despite wide clinical use since the mid-1980s, tiapride was recently withdrawn from the Dutch market without rationale. Although alternatives are available, many patients experienced dysregulation after this unwanted change. We provide insight into the impact of sudden tiapride withdrawal by reviewing medical records of HD patients who were using tiapride at the time of withdrawal. In addition, we performed a systematic search in five databases on tiapride efficacy and its safety profile in HD. Original research and expert opinions were included. In our patient group on tiapride, 50% required tiapride import from abroad. Regarding the review, 12 articles on original datasets and three expert opinions were included. The majority of studies showed an improvement in chorea while patients were on tiapride. Due to limited sample sizes, not all studies performed statistical tests on their results. Fifty percent of clinical experts prefer tiapride as initial chorea monotherapy, especially when comorbid behavioral symptoms are present. Side effects are often rare and mild. No safety concerns were reported. In conclusion, tiapride is almost irreplaceable for some patients and is an effective and safe chorea treatment in HD. Show less
Huntington’s disease (HD) is an autosomal, dominant inherited neurodegenerative disorder, characterized by a triad of symptoms including motor abnormalities, behavioral symptoms and cognitive... Show moreHuntington’s disease (HD) is an autosomal, dominant inherited neurodegenerative disorder, characterized by a triad of symptoms including motor abnormalities, behavioral symptoms and cognitive decline. As exact knowledge of the course of cognitive decline and the underlying cause of developing apathy is still lacking in HD, the primary aim of this thesis was to gain further insight into the cognitive profile and apathy in Huntington’s disease (HD). We aimed to evaluate whether the most commonly used participant classification makes a useful distinction between HDGECs and whether these groups are homogeneous by giving an overview of the participants’ characteristics at the largest REGISTRY HD center (chapter 2). In chapter 3, we aimed to map the cognitive profile in different disease stages, and to evaluate whether CAG length mediates cognitive decline in HD (chapter 3). In addition, we explored whether there is a difference in cognitive performance between individuals taking medication targeting non-cognitive neuropsychiatric signs or/and tetrabenazine and non-users in HD (chapter 4). In chapter 5, we aimed to relate apathy to the neurodegenerative process in HD. In chapter 6, we evaluated whether HDGECs and their proxies agree on the degree of apathy by using a self-report questionnaire. Show less
This thesis demonstrates the application of bioinformatics to investigate the mechanisms that are implicated in Huntington’s Disease (HD). HD is an inherited neurodegenerative disorder and although... Show moreThis thesis demonstrates the application of bioinformatics to investigate the mechanisms that are implicated in Huntington’s Disease (HD). HD is an inherited neurodegenerative disorder and although the cause of the disease is known since 1993 we are still lacking a cure or treatment that can effectively treat the symptoms of HD. In order to tackle such a complicated case study, we followed a multidisciplinary approach to exploit the expertise and knowledge of people with diverse scientific background (chapter 2). This blend of disciplines facilitates constant collaboration between bioinformaticians, wet lab technicians, biologists, computer engineers and data scientists. A collaborative eScience model is proposed as a way to combine state-of-the-art computation analysis and laboratory work (chapter 3). At the same time, we explored methods to preserve the results, materials and methods involved in the experiment to increase the reproducibility and reusability of our research (chapter 4). In chapter 5 we identified disease signatures in blood that are functionally similar to signatures in brain. These are proposed as candidate biomarkers to be used as a monitoring tool for the state of the disease in brain, but also as a means to determine whether a treatment is successful or not. Show less
Euthanasia and physicia-assisted suicide are possible in case of Huntington's Disease, also based on an advance directive. Requirements to make this possible are a sound and possibly longstanding... Show moreEuthanasia and physicia-assisted suicide are possible in case of Huntington's Disease, also based on an advance directive. Requirements to make this possible are a sound and possibly longstanding physician-patient relationship. Secondly a thorough knowlegde of the requirements of due care is necessary, for patients as well as for physicians. Physicians and patients should both be educated upon the possibilites provided in the law. Show less
The aims of this thesis were to gain insight into specific disease processes in Huntington__s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain... Show moreThe aims of this thesis were to gain insight into specific disease processes in Huntington__s Disease (HD) and to identify biomarkers. To achieve these aims, cognitive functioning, structural brain characteristics and intrinstic functional brain connectivity of premanifest and early HD subjects were examined. Cortical, subcortical and the intermediate white matter brain tissue shows evidence of structural and functional decline. We found evidence that disease processes, such as altered metabolism, excessive iron accumulation and cell loss, play a role in the changes. We conclude that changes occur throughout the brain from the earliest disease phase onwards. Hence, both premanifest and manifest HD should not be regarded as a disorder of the basal ganglia, but as a disease affecting the whole brain. Candidate biomarkers that have the potential to objectively reflect the early changes and the progressive nature of the disease are measures of subcortical atrophy, integrity of white matter pathways and of intrinsic functional brain connectivity. Iron, creatine, and N-acetylaspartate concentrations in the caudate nucleus and putamen may prove to be useful as markers of disease state for objectifying transitional disease processes from premanifest to manifest HD. Visuospatial working memory could be applied as a state marker for stage two HD. Show less
The aim of this thesis was to find potential MRI biomarkers for Huntington__s disease (HD). Therefore, after an overview of the current literature on MRI biomarkers, followed by examinations of... Show moreThe aim of this thesis was to find potential MRI biomarkers for Huntington__s disease (HD). Therefore, after an overview of the current literature on MRI biomarkers, followed by examinations of volumetric MRI, magnetization transfer imaging (MTI), diffusion tensor imaging (DTI) and magnetic resonance spectroscopy (MRS) were applied in patients in different disease stages of HD. The main conclusions demonstrate that choosing the optimal biomarker for evaluating therapeutic effects is dependent on the disease stage and therapeutic compound. To evaluate the premanifest stages of the disease volumetric MRI and DTI are most suitable. When the transition period is the desired timeframe for evaluation, also MRS can be very useful, especially if the compound in question has a direct potential influence on certain pathogenic pathways which in turn have an impact on specific metabolites. Future research should focus on combining multiple imaging techniques; __multimodal imaging__. A composite MRI biomarker has the potential to distinguish between disease groups more accurately than a single biomarker and in this way improve the evaluation of therapeutic compounds. Show less
