Title Promoter Affiliations Abstract "Arm-hand BOOST therapy to enhance recovery after stroke in the sub-acute phase after stroke: clinical evaluation up to one year post-stroke" "Geert Verheyden" "Research Group for Neurorehabilitation (eNRGy)" "Deficits in arm and hand movements after stroke are common and result in reduced independence in activities of daily living and quality of life. Implementable therapy in the subacute rehabilitation phase for improved arm and hand recovery long-term after stroke that demonstrates robust benefits for patient and society is still required. This is what our project will investigate, specifically whether for P: patients after stroke, who are admitted to inpatient stroke rehabilitation, and who have the potential to relearn, I: an additional, comprehensive, arm-hand intervention (Aha BOOST) C: when compared to dose-matched therapy for the lower limb, O: enhances arm-hand function and activity post-treatment and long-term. For this evaluation, a randomized controlled trial will be conducted in two independent Flemish rehabilitation centres, recruiting 80 patients in total. Our trial methodology is strongly based on a sound rationale, documented in a proof of concept that demonstrated 80% of patients achieving a clinical meaningful improvement in arm and hand function in the Aha BOOST intervention group compared to 0% in the control group after four weeks of therapy. In our definitive trial, 40 patients per group are included and evaluated pre- and post-intervention, three months after intervention and 12 months after stroke to evaluate immediate, retained and long-term clinical effects. Results include upper limb function, capacity, activity of daily living, and participation. Primary analysis and endpoint is the between-group difference in arm and hand ICF activity level from pre- to postintervention." "Europe on Strike: Wildcat Strikes as a pan-European Phenomenon, 1944-1953." "Patrick Pasture" "Modernity & Society 1800-2000, Leuven, Early Modern History (15th-18th Centuries), Leuven" "During the first post-war years, Europe saw thousands of strikes – the great majority of which was of a wildcat character (i.e. not backed by trade union leaderships), short-lived (often lasting no longer than a couple of hours), and inspired by bread-and-butter concerns (with demands for better provisions almost always taking centre stage). Yet, this type of spontaneous and localized strike has by and large gone unnoticed in academic literature, which has shown a strong preference for politically more “significant” strikes (e.g. the “insurrectional” strikes that swept France in 1947-48). My project, conversely, takes wildcat strikes as its point of departure. I aim to write a comparative social history of the wildcat strike movement hitting the European continent (both in Eastern and Western Europe) following World War Two – with a focus on wildcat strikes in Belgium, Czechoslovakia, West Germany, Italy, and Poland. My project addresses a broad range of themes, including gender history (exploring how trade union leaders grappled with this frequently women-led protest form) and the history of racism (exploring how striking workers often attributed the problems of their local community to ethnic outsiders). Above all, however, by focusing on spontaneous, wildcat strikes, my project (more so than studies of those strikes stagemanaged by trade unions) provides us with a real insight into the everyday concerns of workers at a crucial juncture in European history." "HPLC analyses in activation of the kynurenine pathway in the acute phase of stroke, and its role in depression and fatigue following stroke." "Dirk Hendriks" "Medical Biochemistry" "This project represents a formal research agreement between UA and on the other hand a private institution. UA provides the private institution research results mentioned in the title of the project under the conditions as stipulated in this contract." "Bimanual performance and life balance one year after stroke. Assessment, evolution and prognosis" "Geert Verheyden" "Research Group for Neurorehabilitation (eNRGy)" "Stroke remains one of the leading causes of disability with loss of independency for daily activities as a long-term consequence. The vast majority of daily activities demand the use of both hands working together. Up to 85% of stroke survivors present with upper limb impairment, which may compromise bimanual performance. To date, the vast majority of studies focus on unimanual recovery and provides scarce knowledge about recovery and prognosis of bimanual performance. Bimanual performance may play an important role in the involvement in meaningful activities. Stroke survivors reported that they were challenged to re-engage in meaningful activities, which compromised a well-balanced pattern of activities. Therefore, we introduced the concept of life balance as having a well-balanced pattern of activities. Accordingly, the aim of this doctoral thesis was to gain insight in bimanual performance, life balance and the interaction between both concepts.In the first study, we provided novel evidence regarding reliability and validity of the Adult Assisting Hand Assessment Stroke (Ad-AHA Stroke). This assessment, originally developed to evaluate the use of the affected hand in bimanual task performance in a pediatric population, was previously adapted for use in people with stroke. We demonstrated substantial to excellent reliability and a low standard error of measurement (SEM) for intrarater and interrater agreement respectively in 30 participants. The hypothesis that a high correlation would be found between bimanual performance and unilateral motor function supporting convergent validity, was confirmed in 118 participants. Of note, we found a relatively high variability at the higher and lower end of the Ad-AHA Stroke score range in relation to unilateral motor function, providing evidence that the Ad-AHA Stroke measures a different construct than unilateral motor function. We were able to demonstrate support for discriminative validity, differences in Ad-AHA stroke scores were found between participants with visuospatial neglect and without visuospatial neglect and between participants with the dominant hand affected and those with the nondominant hand affected.In a subsequent study, we identified the prognostic value of baseline variables on bimanual performance in a cohort of stroke survivors (n=92) until one year after stroke. Baseline variables were collected within the first week of inpatient rehabilitation and the Ad-AHA Stroke was administered at six months (n=81) and at one year (n=69) after stroke. Moderate associations between bimanual performance and hand dominance, somatosensory, cognitive and mental function and activity limitations were found, although the latter were not retained in the multiple prediction model. We revealed that grasp function and stroke severity at baseline after stroke were key predictors of bimanual performance at six months and one year after stroke and both are measured by simple and quick to administer measures, commonly used in stroke rehabilitation, which is an important asset for clinical practice.The next step in this research project was to establish test-retest reliability and convergent validity of the Flemish version of the Life Balance Inventory (Fl-LBI) in chronic community-dwelling stroke survivors (n=32). Satisfactory test-retest reliability was demonstrated for total Fl-LBI scores and subscale scores: The SEM and minimal detectable difference (MDD) were small and similar to those of other patient-reported outcomes in the field. Furthermore, moderate associations between Fl-LBI and participation, mobility and emotions provided support for convergent validity. The results of this study showed first evidence that the Fl-LBI has satisfactory test-retest reliability, acceptable standard error of measurement and minimal detectable difference and acceptable convergent validity.Finally, evolution and prognosis of life balance was examined in an observational longitudinal study. Baseline variables were collected within the first week of inpatient rehabilitation and at six months (n=67) and one year (n=59) after stroke, the Fl-LBI was administered. Moderate scores on the Fl-LBI were found at six and at one year after stroke. Small but significant improvement in life balance occurred within the first year after stroke. Mental function and bimanual performance were key predictors of life balance within the first year after stroke.To conclude, this doctoral project has contributed to the field of stroke recovery and occupational therapy by providing knowledge regarding bimanual performance and life balance, and by demonstrating the interaction between both concepts. With that, a relevant contribution to the field was delivered and further research priorities were identified as well. This doctoral thesis is a valid and essential starting point for further research on bimanual performance and life balance after stroke." "The role of EphA4 in neural repair following ischemic stroke" "Laboratory for Neurobiology (VIB-KU Leuven)" "Stroke is a loss of brain function due to an interruption of cerebral blood flow caused by occlusion (ischemic stroke) or hemorrhage1. It is the leading cause of adult disability and it causes one in 10 deaths worldwide2. The only effective treatments are intravenous recombinant tissue plasminogen activator (rt-PA) and mechanical thrombectomy, which have narrow time windows that limit their use to only a small percentage of patients with ischemic stroke3–5. Therefore, new therapeutic strategies remain necessary.During stroke, ischemia initiates various molecular events. Due to the lack of blood flow, neurons do not get sufficient amounts of oxygen and metabolic substrates resulting in decreased energy production, excitotoxicity, accumulation of ions, mitochondrial injury and eventually neuronal apoptotic and necrotic cell death causing impaired sensory and motor functioning1,6. Although stroke damage can be devastating, many patients survive the initial event and undergo some spontaneous recovery, a process that can be enhanced by rehabilitation therapy1. Recovery involves different mechanisms including neuronal repair, neurogenesis, alterations in existing neuronal pathways, and the formation of new neuronal connections7. However, these restorative responses are limited due to the upregulation of various inhibitory molecules including myelin associated proteins, components of the glial scar and increased expression of developmental axonal guidance cues like components of the ephrin system8,9.The ephrin family consists of Eph receptors and ephrin ligands that act as growth inhibitory proteins10,11. One receptor, EphA4, is of specific interest since we have found increased EphA4 protein levels in the ipsilateral and contralateral hemisphere after stroke. This increase starts already at 24 hours and lasts to at least 28 days post-stroke. More specifically, EphA4 expression is upregulated in old sprouting neurons following experimental stroke12,13. In mice with reduced levels of EphA4 or in whom EphA4 downstream signalling pathways have been pharmacologically blocked, functional recovery after experimental stroke is improved14. Furthermore, EphA4 knock out primary cortical neurons show increased neurite outgrowth compared to control cells, suggesting a role of EphA4 in formation of new neuronal projections, a mechanism that enhances stroke recovery14. Additionally, blocking ephrin-A5, a ligand for EphA4, has shown positive effects on neural plasticity and functional outcome after stroke15.Taken together, these findings suggest an important role of EphA4 in stroke recovery. Moreover, the availability of an EphA4 blocking peptide makes this receptor interesting for therapeutic manipulations. However, the underlying mechanisms as well as the best therapeutic window to target EphA4, in combination with rehabilitation training, remain unknown; therefore further research using different stroke models to validate our initial findings and to determine molecular mechanisms is of great interest." "Neutrophil extracellular traps: a novel target in acute ischemic stroke?" "Simon De Meyer" "Cardiovascular Sciences, Kulak Kortrijk Campus, Chemistry, Kulak Kortrijk Campus" "Stroke is one of the leading causes of death sustained disability worldwide. Despite ongoing advances in stroke imaging and treatment, ischemic and hemorrhagic stroke continue to debilitate patients with devastating outcomes at both the personal and societal levels. Ischemic stroke is caused by a thrombotic obstruction in one major or multiple smaller arteries impairing blood flow to the brain. This results in irreversible damage of brain tissue. Strikingly, the paramount medical relevance of ischemic stroke is in strong contrast to the limited treatment options that are currently available in the stroke clinic. Indeed, only one therapeutic treatment option is currently approved: rapid thrombolysis of the occluding thrombus using tissue-plasminogen activator (t-PA). However, use of t-PA has many serious limitations, including risk of bleeding, narrow therapeutic time window and neurotoxic effects. For unknown reasons, use of t-PA leads to the dissolution of occluding thrombi in some cases, but not in others, suggesting that other unknown partners may be involved in thrombus stability. In fact, it is surprising how little is known about the exact composition of thrombi that cause ischemic stroke. Although timely recanalization of the occluded cerebral artery is fundamental to salvage threatened ischemic tissue, reperfusion of the ischemic territory can also seriously exacerbate tissue damage by reperfusion injury, further worsening clinical outcome. Even though reperfusion injury is clinically very important, the underlying cellular and molecular interactions are still poorly understood. The “thrombo-inflammatory” nature of stroke, involving a complex interplay between both thrombotic and inflammatory processes, has been widely accepted. An intriguing new link between thrombosis and inflammation has just recently been discovered: neutrophil extracellular traps or NETs. A growing body of evidence reveals that NETs also form in human thrombosis and that NET biomarkers in plasma reflect disease activity. The role of NETs in stroke has not been investigated to date. The general aim of this project is therefore to investigate the involvement of NETs in ischemic stroke. We will use experimental mouse models of stroke as well as clinically relevant samples obtained from stroke patients." "Understanding and alleviating the mismatch between observed and perceived upper limb function after stroke" "Geert Verheyden" "Research Group for Neurorehabilitation (eNRGy), Universität Zürich" "In people post stroke, we recently reported a mismatch between observed and perceived upper limb function, i.e. a group of patients at six months after stroke showed good upper limb function but low perceived ability. Building on this knowledge, this project will systematically address the subsequent research questions arising from our previous analysis. Through a longitudinal observation of evolution of mismatch between six and 12 months post stroke, the project will give insight into whether this group of patients with a mismatch increases over time. By investigating the relation between mismatch at six and 12 months and variables on admission to inpatient rehabilitation, this proposal will identify key predictors early after stroke for risk of mismatch in the chronic stage. A crosssectional study to understand the relation between mismatch and actual daily use of the upper limb through sensor technology will provide pivotal information on daily arm use in this group of chronic stroke patients. Finally results from an integrative randomized controlled cross-over trial, with clinical, patient-reported and sensor technology outcomes, examining a two-week boost therapy program for patients with this mismatch between observed and perceived upper limb function, will impact on therapy care of these patients in the chronic phase after stroke. " "In English: REMOTE: The added value of mobile technology for the early detection of atrial fibrillation in the care path of cryptogenic stroke patients" "Pieter VANDERVOORT" "Cardio & organ systems" "Cryptogenic stroke and transient ischemic attack (TIA) patients have no determined etiology at discharge and comprise 25-30% of all stroke and TIA patients. Atrial fibrillation (AF) is a risk factor for stroke and TIA that often goes undetected. AF-related strokes have a higher burden on the patient and the healthcare system. Furthermore, stroke recurrence remains a substantial problem as 9% of patients endure a recurrence after six months, and 14-21% after two years. The risk of AF can be considerably reduced by oral anticoagulation (OAC). However, AF has to be documented for at least 30 seconds prior to OAC therapy initiation. Insertable cardiac monitors (ICMs) are the state-of-the-art as they continuously monitor the heart rhythm for three years. However, due to their high costs and invasiveness, they are underutilized. Therefore, mobile health (mHealth) can be a feasible alternative to ICMs to reduce the risk of stroke recurrence due to AF. In this project, we will determine the added value of mHealth in the care path for the early detection of AF in cryptogenic stroke patients. Therefore, the current view of mHealth in follow-up will be investigated. The yield of AF detection using mHealth and the associated costs will be determined. Finally, the risk stratification that could improve the care path will be identified. As such, this new proof-of-concept care path can lead to improved treatment and a decrease in recurrence, patient morbidity and mortality." "Diagnostic and therapeutic approaches in stroke patients with atherosclerosis" "Laboratory for Neurobiology (VIB-KU Leuven)" "Stroke is a heterogenous condition with many possible causes. In up to 20% of ischemic stroke patients, atherosclerotic disease is found as the underlying cause (i.e. a large vessel disease). Patients with large artery atherosclerosis are at high risk of early recurrence of stroke.In acute iscemic stroke due to intracranial large vessel occlusions (LVOs), tandem occlusions are seen in approximately 20% of patients undergoing endovascular treatment (EVT) for stroke. A tandem lesion is defined as the combination of an intracranial LVO and a high-grade stenosis of the ipsilateral cervical carotid artery. Up to 60-70% of these lesions are due to atherosclerosis. Variation in clinical practice exists regarding the timing of the management of these lesions. Immediate carotid artery stenting (CAS) during EVT could improve cerebral blood flow, reduce the risk of early stroke recurrence and avoid a second procedure (carotid endarterectomy [CEA] or CAS). The CASES trial (Carotid Artery Stenting during EVT of acute ischemic Stroke) aims to evaluate the efficacy and safety of immedaite CAS during EVT. As trial coordinator, I am responsible for the overall management of the CASES trial. One of the main focuses in chronic atherosclerotic carotid artery disease is a better risk stratification of patients with so-called vulnerable plaques in order to enable more patient-specific treatment recommendations. In addition to the degree of stenosis, other plaque characteristics have been associated with increased risk of ischemic events such as intraplaque hemorrhage, intraplaque neovascularization, presence of a lipid-rich necrotic core or a thin fibrous cap, plaque thickness and presence of plaque ulceration and inflammation. Different imaging modalities can be used to visualize these features such as computed tomography angiography (CTA), magnetic resonance imaging angiography (MRA) and molecular imaging (e.g. 18F-FDG Positron Emission Tomography [PET])I want to further investigate the potential of several CTA-derived markers of plaque vulnerability in future risk stratification of patients with mild-to-moderate carotid artery stenosis and recent TIA/stroke. I will also evaluate whether molecular imaging with 18F-AlF-OC PET/MRI has the potential to characterize and quantify carotid atherosclerotic disease manifestations in patients with moderate carotid artery stenosis and recent TIA/stroke." "Behavioral and brain connectivity analysis of upper limb sensorimotor rehabilitation post stroke" "Geert Verheyden" "Research Group for Neurorehabilitation (eNRGy)" "Stroke causes brain damage leading to brain reorganization and motor deficits in the upper limb. The reorganization of the brain after stroke is currently poorly understood. Motor deficits are well documented in the literature but in order to move the arm and hand, so called somatosensory information like knowing the position of your arm and hand in space is necessary. In previous research, we were able to show that motor and somatosensory deficits post stroke are common and related, and thus that therapy for the impaired arm and hand should include both motor and somatosensory exercises. In this study, we therefore investigate whether four weeks of additional physical therapy for the arm and hand offered to people with stroke with an emphasis on motor and somatosensory exercises is more beneficial than four weeks of additional physical therapy consisting of only motor exercises. We will ask from our people with stroke standard arm and hand tasks in order to see whether there is a difference after the additional exercises. Furthermore, we ask our subjects to undergo a brain examination in a standard hospital scanner in order to evaluate brain reorganization due to stroke as well as due to the exercises we provided. With this study, we will gain new knowledge about the reorganization of the brain after stroke as well as the effect of specific exercises on moving arm and hand and brain reorganization, allowing us to design better rehabilitation for arm and hand after stroke."