The prevalence of cardiovascular diseases has increased in the last decennia. This thesis studied the potential relationship between oxidative stress and cardiovascular diseases. The first part of... Show moreThe prevalence of cardiovascular diseases has increased in the last decennia. This thesis studied the potential relationship between oxidative stress and cardiovascular diseases. The first part of the thesis focused on anti-oxidants, which are scavengers that protect against oxidative damage. We studied the association between several lifestyle factors, diet, physical activity, sleep, alcohol intake and smoking, and antioxidant levels both in blood and urine. Subsequently, we investigated whether a higher concentration of antioxidants leads to a decrease in ischaemic stroke occurrence. Next, we aimed to study a possible cause of oxidative damage and its effect on cardiovascular disease. Mitochondrial dysfunction is one of the mechanisms that may underly this effect. Mitochondria are an important source of Reactive Oxygen Species (ROS), as an inevitable byproduct of their essential role in energy production. A disbalance in ROS production and scavenging might result in oxidative damage. Thus, we investigated the causal association between mitochondrial dysfunction and stroke using the Mendelian Randomization method. Finally, we studied how socio-demographic traits could modify the causal association between CVD risk factors and coronary artery disease. Show less
Stroke is one of the leading causes of disability and death worldwide. Prevention of stroke is therefore essential. Effective prevention should be tailored to the clinical characteristics,... Show moreStroke is one of the leading causes of disability and death worldwide. Prevention of stroke is therefore essential. Effective prevention should be tailored to the clinical characteristics, lifestyle, and environment of the individual, among others. This is also known as precision prevention. An important example illustrating the need for precision prevention is the existence of sex differences in stroke occurrence. In practice, for predicting stroke risk, only traditional risk factors (such as smoking and hypertension) are included, and women-specific risk factors are not yet routinely included. As a result, women with an increased risk of stroke may be missed, which also prevents timely initiation of preventive treatments. In this thesis, I tried to lay the foundation for precision prevention of stroke in women.Part I discussed the pathophysiology underlying women-specific risk factors for stroke, and gender differences in the clinical presentation of stroke. I found that the mechanisms underlying the relationship between women-specific risk factors and stroke, in particular the relationship between migraine and cerebral infarctions, seem to be particularly significant in the childbearing phase of life.In Part II, I described how health data from the EHR can be used to develop prediction models for the risk of myocardial infarction or stroke specifically for women under 50 years of age, and found that women-specific risk factors can add value in the predictions. However, there is still a long way to go to actually implement these models in practice, such as testing them on new datasets, and complying with current laws and regulations for safe application. Show less
This thesis describes the wide range of long-term consequences in stroke patients who received multidisciplinary rehabilitation.Over a third of them reported pain in the shoulder, arm, wrist or... Show moreThis thesis describes the wide range of long-term consequences in stroke patients who received multidisciplinary rehabilitation.Over a third of them reported pain in the shoulder, arm, wrist or hand. About the same percentage had low patient activation scores, which is a prerequisite for effective self-management to cope with the consequences of stroke. Almost half of patients who were working before the stroke managed to maintain paid employment for two and a half years. These patients were more satisfied with their participation than patients who did not return to work. Average independence in daily activities increased during rehabilitation. The Barthel Index was found to be more sensitive to measure change than the Utrecht Scale for Evaluation of Rehabilitation. Health-related quality of life increased on average from start of rehabilitation to one year afterwards. The average social costs in the first year were €63,045 for inpatients and €24,533 for outpatients. The burden of the nearest of stroke patients was investigated, which showed that a third of them experienced a high burden.In conclusion, the consequences of stroke can also remain present, worsen or develop in the long term and are present for the individual patient, their nearest and the healthcare system. Show less
Stroke is a relatively common condition with a large impact on patients’ lives. Rehabilitation treatment aims to support patients in coping with the physical, mental, cognitive and social... Show moreStroke is a relatively common condition with a large impact on patients’ lives. Rehabilitation treatment aims to support patients in coping with the physical, mental, cognitive and social consequences of stroke. Recently, there is an increasing interest in the application of digital technologies (eRehabilitation) in healthcare in general, including in stroke rehabilitation. ERehabilitation may include physical and cognitive exercise programs, patient information and education, e-consultations, physical activity tracking and serious gaming, preferably all together in one digital environment.Although there is evidence on the effectiveness and feasibility of eRehabilitation, the uptake of eRehabilitation in specialized stroke rehabilitation facilities has been slow, warranting the need for implementation research. The aim of this thesis was to provide insight in the complex interplay between the effectiveness, the implementation strategy and the context of eRehabilitation after stroke, as delivered in a specialized rehabilitation facility, in order to improve future use of eRehabilitation in specialized stroke rehabilitation facilities. Show less
Stroke is one of the leading causes of mortality and morbidity in the world. Stroke can be divided in ischemic stroke and hemorrhagic stroke. Ischemic stroke is most often caused by an acute... Show moreStroke is one of the leading causes of mortality and morbidity in the world. Stroke can be divided in ischemic stroke and hemorrhagic stroke. Ischemic stroke is most often caused by an acute occlusion of one of the cerebral arteries. Acute stroke treatment aims at resolving these acute artery occlusions. This can be done with intravenous thrombolysis or with locally applied therapy, i.e. intra-arterial, with thrombolytics or mechanical thrombectomy. This thesis focuses on the evolution of intra-arterial stroke treatment in the Netherlands. It captures the period before publication of the large randomised controlled trials that would eventually lead to implementation of intra-arterial treatment as standard treatment for patients with acute ischemic stroke caused by large cerebral artery occlusion. 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
In upper motor neuron diseases, like spinal cord injury, cerebral palsy and stroke, motor areas in the brain and/or spinal cord are damaged or fail to develop normally. Patients suffer from... Show moreIn upper motor neuron diseases, like spinal cord injury, cerebral palsy and stroke, motor areas in the brain and/or spinal cord are damaged or fail to develop normally. Patients suffer from increased joint stiffness, diminished range of motion and flexion deformity. The underlying neural reflexive and non-neural tissue (i.e. muscle slack length and stiffness) contributors of these motor disorders cannot be distinguished by current clinical tests. This distinction of contributors is however important for treatment selection and to understand the mechanism of functional recovery. To quantify the neural and non-neural contributors, an instrumented electromyography driven non-linear neuromuscular modeling approach was developed, validated and applied in patients with stroke and cerebral palsy. The clinical potential of the modeling approach was illustrated by the development over time of neural and non-neural contributors in the sub-acute phase post-stroke and by the effect of botulinum toxin A treatment on these contributors in chronic stroke patients. The results from longitudinal assessments are a step forward in answering “when” to treat a stroke patient. The results also give direction to the question “how” to treat stroke patients, i.e. which treatment option is most effective in each individual patient. Both are a prerequisite for personalized treatment. Show less
In een cross-sectioneel onderzoek is nagegaan hoe het op de lange duur met CVA patiënten gaat die in het Haaglanden Medisch Centrum te Den Haag opgenomen zijn geweest vanwege een beroerte. Er is... Show moreIn een cross-sectioneel onderzoek is nagegaan hoe het op de lange duur met CVA patiënten gaat die in het Haaglanden Medisch Centrum te Den Haag opgenomen zijn geweest vanwege een beroerte. Er is gekeken naar verschillende aspecten zoals handfunctie, werkhervatting, stemmingsproblemen en zorggebruik. Het blijkt dat, ondanks alle behandelingen die gegeven worden, een grote groep van deze mensen restbeperkingen ervaart. Hun partners voelen zich fors belast, vooral als er sprake is van stemmingsproblemen en als werkhervatting niet lukt. Ook jaren later geeft de meerderheid van CVA patiënten aan nog steeds zorgvragen te hebben die niet beantwoord zijn. Ze lijken beter hun weg te vinden in de eerstelijn voor hun fysieke problemen dan voor hun mentale problemen. Er is gekeken naar de mate waarin eerstelijns behandelaars zich hebben georganiseerd met betrekking tot chronische behandeling en begeleiding van CVA patiënten. Een goed georganiseerd netwerk, met een visie op kwaliteitsaspecten en scholing, is maar op enkele plaatsen in het land beschikbaar. Er zijn aanbevelingen geformuleerd om de ontwikkeling van eerstelijns netwerken voor CVA patiënten te stimuleren. Show less
The aim of this thesis was to explore the neuromechanics of recovery of arm-hand function after stroke. A literature review revealed six articles that measured biomechanical and electromyographical... Show moreThe aim of this thesis was to explore the neuromechanics of recovery of arm-hand function after stroke. A literature review revealed six articles that measured biomechanical and electromyographical outcome measures simultaneously, while applying active and passive tasks and multiple movement velocities to separate neural and non-neural contributors to movement disorders after stroke. Therefore, a neuromechanic assessment protocol was developed. Parameters were responsive to clinical status and had good to excellent test-retest reliability. Selective muscle activation was assessed with high measurement reliability and was significantly lower in chronic stroke patients compared to healthy participants. Longitudinally, neuromechanical parameters were combined with data on arm-hand function at six months after stroke. Paresis and diminished modulation of reflexes were associated with poor functional outcome. Changes in tissue properties were represented by a shift in wrist rest angle towards flexion and decline in passive range of motion. Increase in active range of motion and steady rest angle contributed most to prediction of functional outcome. The precision diagnostics provided by a neuromechanical assessment protocol could support clinical decision making and should be used in prediction models and as biomarkers in recovery of arm-hand function after stroke, for example by improving the selection of time-window and patients. Show less
The main objective of this thesis was to evaluate the role of new advanced multimodal CT imaging techniques in acute ischemic stroke.Important findings are that collateral assessment with dynamic... Show moreThe main objective of this thesis was to evaluate the role of new advanced multimodal CT imaging techniques in acute ischemic stroke.Important findings are that collateral assessment with dynamic CT angiography (CTA) better predicts radiological outcome and clinical outcome compared with conventional single-phase CTA. Dynamic CTA also enabled us to study dynamic cortical venous outflow in stroke which had not been described before. We have shown that venous outflow, as assessed with dynamic CTA, is a new predictor of functional outcome in acute large vesselvanterior circulation stroke. By combining the extent and velocity of optimal CVF, we observed a decreased risk of poor outcome in patients with good and fast optimal CVF. Moreover, we have demonstrated an interaction between IAT treatment effect and cortical venous filling which could potentially be useful for future treatment decision-making. Show less
The research in this thesis was aimed at investigating the central hypothesis that susceptibility to SD determines both the susceptibility to migraine with aura and the susceptibility to... Show moreThe research in this thesis was aimed at investigating the central hypothesis that susceptibility to SD determines both the susceptibility to migraine with aura and the susceptibility to hypoxic/ischemic injury in the same direction. We envisage that factors that enhance the susceptibility to SD increase the likelihood of migraine with aura as well as ischemic stroke. To this end we assess to what extent genetic, hormonal and pharmacological modulators of SD susceptibility will influence the susceptible to ischemic injury. Thus we will unravel underlying mechanisms of SD susceptibility and susceptibility to ischemic injury. Central to this research is the use of two transgenic mouse models of migraine that carry migraine-relevant FHM1 gene mutations in voltage-gated CaV2.1 Ca2+ channels. Show less
The objective of this thesis was to elucidate whether migraine is a true and independent risk factor for brain lesions. We summarized migraine symptoms, diagnostic criteria, epidemiologic data, and... Show moreThe objective of this thesis was to elucidate whether migraine is a true and independent risk factor for brain lesions. We summarized migraine symptoms, diagnostic criteria, epidemiologic data, and assumed pathophysiology. We described the existing literature on the relationship between migraine and ischemic stroke and cerebral white matter lesions (WML). The findings of the population-based CAMERA MRI-study are reported. Posterior circulation (cerebellar) infarcts occurred in 8% of migraineurs with aura (adjusted-OR 13.7). Female migraineurs were at increased risk of high-deep-WML-load (OR 2.0). Risks increased with attack frequency, suggestive of a causal relationship. We detailed on the infarcts and other infratentorial lesions. Findings of higher iron-concentration in deep brain nuclei in younger migraineurs suggest that repeated migraine attacks are associated with changes in regions known to be involved in central pain processing and migraine pathophysiology. In addition, we showed that migraineurs had more syncope-related autonomic-nervous-system symptoms, and we identified frequent syncope and orthostatic insufficiency as independent risk factors for high-DWML-load. With these data, there is now strong evidence that migraine is indeed an independent risk factor for silent brain lesions. The real extent of brain injury in migraine patients in the general population is likely underestimated. Show less
