The aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into... Show moreThe aim of this thesis was to assess the efficacy (part 1) and tolerability (part 2) of antiseizure medications (ASMs) in glioma patients with epilepsy. In addition, we aimed to get insight into the ASM prescription behavior and treatment policy in brain tumor-related epilepsy (part 3).First-line levetiracetam seems to be the most efficacious ASM in glioma patients, with favourable tolerability. This is demonstrated in multicenter retrospective observational cohort studies, a systematic review, and is the opinion among the vast majority of European neuro-oncology professionals. Enzyme-inducing AMSs should be avoided in glioma patients due to the high risk of adverse effects. ASM use was not independently associated with neuropsychiatric symptoms in glioma patients, but alternative factors seem to pose a greater risk for developing neuropsychiatric symptoms. If patients experience uncontrolled seizures on ASM monotherapy, levetiracetam combined with valproic acid has better efficacy than other ASM combinations in glioma patients, while toxicity is similar. Subsequently, potential add-on ASMs in glioma patients experiencing uncontrolled seizures on ASM dual therapy include clobazam, lamotrigine, and lacosamide. Show less
This thesis reinforce that children born preterm are at risk for long-term impairments. Being able to predict who is at risk, by neonatal neuroimaging or early assessment, remains difficult,... Show moreThis thesis reinforce that children born preterm are at risk for long-term impairments. Being able to predict who is at risk, by neonatal neuroimaging or early assessment, remains difficult, especially in children who have milder forms of brain injury and/or experience milder difficulties at two years of age. Currently, most follow-up assessments use standardized outcome measures that might not show the full extent of a child’s daily functioning. Additional measurements and/or the implementation of qualitative research can be of great additional value. Show less
The aim of this thesis is to explore fear of choking and fear of falling in people with Huntington's disease (HD) and their caregivers. Dysphagia and falls are common in HD and may lead to fear of... Show moreThe aim of this thesis is to explore fear of choking and fear of falling in people with Huntington's disease (HD) and their caregivers. Dysphagia and falls are common in HD and may lead to fear of choking and fear of falling. However, knowledge about this is mostly lacking, as well as knowledge about the relationship between cognitive and emotional factors and these types of fear. The study confirms that fall prevalence (29% over a 30-day period) and prevalence of dysphagia symptoms (90%) are high. However, a prevalence of about 50% is also reported for fear of choking and fear of falling in people with HD. However, their informal caregivers report the most fear. Severity of dysphagia symptoms was a predictor of fear of choking, and anticipatory awareness of fall risks and gender were found to be predictors of fear of falling. In most individuals with HD, a combination of preventive measures was used.Future research can improve both management of dysphagia and fear of choking and management of falls and fear of falling. Because questioning people with HD is sometimes difficult, due to speech and cognitive difficulties, diagnostic tools may be sought to facilitate this, such as wearable electronic devices. Show less
This thesis describes studies of individuals with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms at the Leiden NPSLE clinic. A diverse range of studies, including... Show moreThis thesis describes studies of individuals with systemic lupus erythematosus (SLE) presenting with neuropsychiatric (NP) symptoms at the Leiden NPSLE clinic. A diverse range of studies, including laboratory, radiological, clinical and patient´s reported outcomes are presented.The Leiden NPSLE clinic is a tertiary referral center for patients with SLE and neuropsychiatric (NP) symptoms. In the NPSLE clinic, patients are assessed by a multidisciplinary team. Thereafter, clinical, radiological and laboratory measures are weighed in a consensus meeting to correctly attribute the NP symptoms: related to lupus activity (NPSLE) or not. This extensive and standardized assessment of NPSLE, a rare and heterogenous disease lacking a gold standard, is unique and creates the opportunity to explore many aspects of NPSLE in well-defined phenotypes.In the first part of this thesis, we evaluate both classification and treatment of patients withSLE and NP symptoms. The second part of this thesis focuses on a diverse range of clinicaloutcomes of NPSLE, including both morbidity and mortality. The last part of this thesisassesses potential biomarkers for (specific manifestations of) NPSLE. Show less
Patients with Parkinson's Disease may be eligible for Deep Brain Stimulation (DBS) in case of severe motor complications. This thesis provides indications for improving patient selection for DBS,... Show morePatients with Parkinson's Disease may be eligible for Deep Brain Stimulation (DBS) in case of severe motor complications. This thesis provides indications for improving patient selection for DBS, as well as describing new biomarkers based on Electroencephalography (EEG) to aid during the DBS selection process. Show less
We aimed to expand our knowledge about the level of neurocognitive functioning (NCF) and health-related quality of life (HRQoL) in patients with primary and secondary brain tumors during the... Show moreWe aimed to expand our knowledge about the level of neurocognitive functioning (NCF) and health-related quality of life (HRQoL) in patients with primary and secondary brain tumors during the disease course. We found that the tumor itself has the largest negative impact on NCF and HRQoL. At group level, treatment (surgery, radiotherapy and/or chemotherapy) did not seem to have a large extra detrimental effect on the short term. However, subgroups of patients, e.g. patients with tumors in the non-dominant hemisphere and long-term survivors, appeared to be vulnerable for cognitive decline after treatment. At the individual patient level, HRQoL varied to a large degree in the first months after treatment, confirming this is a multidimensional concept and that the impact of treatment differs for the different aspects. With the results from the studies described in this thesis, treatment and individual patient care can be optimized by minimizing the negative impact of treatment, e.g. by intraoperative monitoring of cognition during awake surgery, and by counseling and rehabilitation of patients. Besides, investigators should pay attention to methodological challenges in reporting of neurocognitive outcomes in research, as reporting of these outcomes is currently not sufficient, while evidence can be of value in clinical decision-making. Show less
The number of older people in the population is rising and so is the number of older patients in the Emergency Department (ED). Older patients often have complex problems which leads to an... Show moreThe number of older people in the population is rising and so is the number of older patients in the Emergency Department (ED). Older patients often have complex problems which leads to an increased change of repeat ED visits, longer length of stay, higher chance of hospital admission and higher chance of negative health outcomes. Cognitive impairment is a frequent problem in older ED patients but often remains unrecognized and little is known about the association between cognitive impairment and adverse outcomes in older ED patients. In this thesis we show that cognitive impairment is associated with adverse outcomes in acutely presenting older patients. Secondly, we show that routinely collected parameters in addition to cognitive impairment can be used to screen for high risk of adverse outcomes in older ED patients. We investigated two delirium screeners and showed the CAM-ICU might not be suitable for early detection of delirium in the ED. Finally, vital signs that associate with decreased brain perfusion and oxygenation, such as low systolic blood pressure, were associated with cognitive impairment in older ED patients. Next steps would be to investigate if optimal resuscitation might improve cognition and decrease risk of subsequent delirium and adverse outcomes. Show less
This thesis focused on the evaluation of an eHealth intervention for cognitive stroke rehabilitation and the perspectives of different stakeholders on the uptake of eRehabilitation in general. The... Show moreThis thesis focused on the evaluation of an eHealth intervention for cognitive stroke rehabilitation and the perspectives of different stakeholders on the uptake of eRehabilitation in general. The studies included in this thesis showed that there was no overall effect of an online brain training programme on cognitive functioning of patients with stroke. Only performances on cognitive function tests that were similar to the games included in the intervention improved, no near transfer effect was found. Moreover, usage of the training was suboptimal and not all of the patients were able to complete it. It would appear important to support stroke patients with CBCR training, since training is not well used by all patients. However, regarding patients’ ICT readiness, wishes and requirements it was also found that a relatively large amount of patients in rehabilitation wish to incorporate ICT in their rehabilitation treatment. In addition, developing tailored implementation strategies to implement eHealth in the bachelor curriculum of health professionals, based on the identified barriers and facilitators in this thesis is highly relevant to make sure that future health professionals are able to work with eHealth. Show less
Huntington’s disease (HD) is a progressive autosomal dominant inherited neurodegenerative disorder.The primary aim of this thesis is to examine alterations in the cerebral cortex in HD gene... Show moreHuntington’s disease (HD) is a progressive autosomal dominant inherited neurodegenerative disorder.The primary aim of this thesis is to examine alterations in the cerebral cortex in HD gene carriers. Different image modalities and approaches will be used to extent the knowledge on both structural and functional cortical brain changes in early disease. Although striatal atrophy is more extensively present in HD, changes in the cerebral cortex can also be detected in the pre-symptomatic stage. Different methodological approaches used in our studies all showed a consistent pattern of cortical atrophy making volumetric MRI a reliable and effective tool to assess early in-vivo cortical brain changes, even in a rare neurodegenerative disorder such as HD. The influence of cortical changes on other clinical signs that occur in HD should not be overlooked. Our results demonstrate that volume loss and thinning of the cerebral cortex, especially the posterior brain regions, is detectable in early stages and contributes to the presence of specific motor signs and cognitive impairments. We believe that intervention trials could benefit from using cortical volumes as outcome measures, instead of using striatal volumes alone. Show less
The aim of this thesis is to examine employment and driving ability in gene carriers with Huntington’s disease (HD). HD is an autosomal-dominant inherited neurodegenerative disorder and manifests... Show moreThe aim of this thesis is to examine employment and driving ability in gene carriers with Huntington’s disease (HD). HD is an autosomal-dominant inherited neurodegenerative disorder and manifests during mid adulthood. The disease is clinically characterized by motor disturbances, cognitive decline and behavioral changes. Since there is currently no cure for HD, the focus of treatment is on improving quality of life and providing the necessary support to patients and families. Maintaining independence through employment and driving, for as long and as safely as possible, has a substantial influence on a patient’s general functioning. Our results consistently showed that the cognitive and behavioral changes of HD are more debilitating in daily life than the characteristic motor signs, and are associated with employment and driving a car. Healthcare professionals should be educated about HD to allow them to provide appropriate information to patients and families when discussing possible changes in working and driving as a result of HD. Individual evaluation of driving ability is warranted and the recommendation to stop driving should not solely be based on disease stage or a genetic confirmation. Multidisciplinary screening, using a HD-specific test battery, is recommended and should be embedded in the clinic. Show less
With increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year... Show moreWith increasing age, blood pressure (BP) rises as a consequence of arterial stiffness. It has been debated whether it is beneficial to treat hypertension in old age especially in >75-year-olds when they have multimorbidity, polypharmacy or frailty. Large trials showed that lowering BP in >60-year-olds is beneficial and lowers the risk for myocardial infarction, stroke and all-cause mortality. However, these trials lack generalizability and typically excluded multimorbid patients that are frail. At the same time, observational studies rose concerns about lowering BP too much since there are several cohort studies showing a reverse association of low BP and increased mortality especially in >75-year-olds. The general aim of this thesis is to increase the scientific knowledge about the effects of treating hypertension in >75-year-olds with frailty. This thesis has three aims: 1) to measure the prevalence of polypharmacy in older patients; 2) to test for an association between low SBP and mortality, cognitive function, daily functioning, and QoL in older patients under antihypertensive treatment; and 3) to understand the role that frailty plays in GP decisions about treating hypertension in old age across countries and see if those differences can be explained by country-specific cardiovascular disease burden and life expectancy. Show less
This thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2,... Show moreThis thesis investigates different aspects of apathy - as a distinct clinical syndrome assessed with the Apathy Scale- in older persons with and without concurrent depression. In Chapter 2, clinically relevant subtypes of apathy according to the Apathy Scale in older persons from the PROMODE study are examined, using data-driven Latent Class Analysis (LCA). Further, specific characteristics across the classes identified by LCA are investigated. Then, in Chapter 3, cross-sectionally the prevalence, severity and clinical profile of apathy in depressed and non-depressed older persons, in relation to various possible determinants is described. Chapter 4 examines which characteristics predict, over a 2-year period, the incidence and course of apathy in at baseline depressed older persons from the NESDO study. Chapter 5, using data of the NESDO and NESDA, investigates the presence of apathy in late-life compared to early-life depression, and various determinants of clinically relevant apathy in older compared to younger depressed persons. In Chapter 6 the association of the presence of apathy among community-dwelling older persons from the PROMODE study and a diminished quality of life is examined. All results are placed a current perspective in Chapter 7 that also discusses clinical implications, and makes some recommendations for future research. Show less
This thesis describes several state-of-the-art challenge methods to study the cholinergic system in humans by measuring the effects of compounds that selectively act upon muscarinic or... Show moreThis thesis describes several state-of-the-art challenge methods to study the cholinergic system in humans by measuring the effects of compounds that selectively act upon muscarinic or nicotinic acetylcholine receptors. The thesis reveals part of the complexity of the cholinergic system, its changes related to aging, its relationship with cognitive function and performance, and its role in inflammation. Additionally, the methodology described in the thesis provides controlled circumstances using repeated measurement of drug concentrations and effects during a pharmacologic cholinergic challenge that can be used in drug development of new compounds with cholinergic activity. Show less
