Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

This thesis presents three novel PET targets in stroke research.First we explore amyloid PET in the context of cerebral amyloid angiopathy. Cerebral amyloid angiopathy is a frequent cause of lobar intracerebral hemorrhage and is characterized by vascular amyloid β accumulation. Amyloid tracers, which were originally developed in the setting of Alzheimer disease, do not only bind to parenchymal amyloid plaques (as seen in Alzheimer disease), but also to vascular amyloid. Therefore, they can also visualize amyloid accumulation related to cerebral amyloid angiopathy. In chapter 1, we retrospectively focus on the value of amyloid PET in patients with lobar intracerebral hemorrhage, as we believe that the modified Boston criteria, which are currently seen as gold standard to diagnose cerebral amyloid angiopathy in vivo, have certain drawbacks in this population. We posit that - despite prior studies showing only moderate diagnostic accuracy of amyloid PET in diagnosing cerebral amyloid angiopathy - further research is needed just because most prior studies relied on the modified Boston criteria. We hypothesize amyloid PET to be a valuable tool to diagnose cerebral amyloid angiopathy in certain patients. In chapter 2, we describe a case series of patients presenting with cerebrovascular disease < 55 years old in whom (transmissible) cerebral amyloid angiopathy is the most likely diagnosis. Transmissible cerebral amyloid angiopathy is a - still controversial - entity marked by human-to-human transmission of amyloid β. Patients who undergo neurosurgery during childhood can present with cerebral amyloid angiopathy at relative young age, making it impossible to diagnose with the current modified Boston criteria. To assess its prevalence, large epidemiological studies are needed and we propose amyloid PET as non-invasive tool for in vivo diagnosis of transmissible cerebral amyloid angiopathy.Second we use tau PET to evaluate if ischemic stroke triggers formation of neurofibrillary tangles, thereby (partially) explaining the increased risk of Alzheimer disease after stroke. 18F‑MK‑6240 is a second generation tau tracer that specifically binds to neurofibrillary tangles. In chapter 3, we discuss a prospective study in which patients with a first ischemic stroke undergo 18F‑MK‑6240 PET within the first weeks and at 6 months after stroke. We notice an increased PET signal within the lesion at baseline, but we stress that its interpretation is complicated by blood brain barrier breakdown. We also demonstrate an increased 18F‑MK‑6240 signal at 6 months after stroke and explain that it is plausible that this increased PET signal reflects specific binding to neurofibrillary tangles, implying that our data provides preliminary evidence of accumulation of neurofibrillary tangles after ischemic stroke.Third we explore neural plasticity after stroke with synaptic density PET. Recovery after stroke is a complex phenomenon of which the underlying biological processes are poorly understood. Neural plasticity, including both reorganization of networks as well as reinforcement of existing connection, has been suggested to drive recovery after stroke. We investigate if 11C‑UCB‑J, a PET tracer that binds to synaptic vesicle protein 2A and is seen as proxy for synaptic density imaging, can visualize neural plasticity after stroke. In chapter 4, we first show that synaptic density is not influenced by age or sex, indicating that age- and sex matching is not too important in stroke studies. Next, we investigate changes in synaptic density after ischemic stroke by prospectively recruiting patients with a first ischemic stroke to undergo 11C‑UCB‑J PET within 2-4 weeks as well as 6 months after stroke. In chapter 5, we describe the baseline data and we illustrate synaptic density to be decreased within the lesion within the first weeks after stroke as well as in the ipsilesional hemisphere. In chapter 6, we report the 6 months follow up data that indicate that no increases of synaptic density can be found in any of the brain regions. However, we demonstrate that synaptic density further decreases in the ischemic lesion as well as in surrounding tissue.In summary, this thesis introduces three novel PET targets in stroke research: one to aid in diagnosing cerebral amyloid angiopathy, a common etiology of hemorrhagic stroke, and two to further expand our knowledge on pathophysiological processes that occur after ischemic stroke.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Background: Multiple studies have focused on the baseline National Institutes of Health Stroke Scale (B-NIHSS) as a predictor of functional outcome after stroke. The change in NIHSS in the first 24h after stroke has been studied as a predictive variable for outcome, but the assessment of clinical improvement has been performed in various paradigms. In this study we intended to determine the accuracy of these different models. Methods: We included 369 patients in a retrospective study based on a database of 492 stroke patients. The NIHSS was calculated on admission and after 24 hours and the delta NIHSS, relative reduction (RR NIHSS) and major neurological improvement (MNI; NIHSS of 0-1 or≥8 point improvement at 24h) were calculated. The outcome at 90 days was measured by the Modified Rankin Score (mRS) and defined as good functional outcome (GFO): mRS of 0 to 2;and excellent functional outcome (EFO): mRS of 0 or 1. Independent predictors of GFO and EFO were identified by multivariate logistic regression. We performed a subgroup analysis after excluding minor stroke patients (NIHSS 0-5) since change in NIHSS at follow-up might be assessed more reliable in patients presenting with a severe deficit. Results: B-NIHSS was associated with both GFO (OR: 0.82; 95CI 0.78-0.86) and EFO (OR: 0.82; 95CI 0.77-0.86) with fair accuracy (AUC for GFO: 0.78, AUC for EFO: 0.75). Change in NIHSS after 24h was associated with GFO (OR:1.76; 95CI 1.07-2.97) and EFO (OR:2.19; 95CI 1.43-3.38) as calculated by the MNI without substantial accuracy (AUC for GFO: 0.57, AUC for EFO: 0.59).When excluding minor strokes B-NIHSS was associated with functional outcome (GFO OR:0.86; 95CI 0.79-0.93, EFO OR:0.88; 95CI 0.79-0.96) with fair to poor predictive value (AUC for GFO: 0.71, AUC for EFO: 0.66). Change in NIHSS had the most optimal accuracy (AUC for GFO: 0.67, AUC for EFO: 0.72)when determined by RR NIHSS which was associated with both GFO (OR: 6.4; 95CI 2.25-20.01) and EFO (OR:12.85; 95CI 3.69-51.55). Conclusion: B-NIHSS was associated with functional outcome with fair accuracy. Changes in NIHSS as assessed by three different definitions had less predictive value. The best predictive value of difference in NIHSS was obtained by MNI. When excluding all minor stroke this change in NIHSS had the most optimal accuracy if calculated by the RR NIHSS.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Inleiding: De rol van chirurgie in hemorragisch cerebrovasculair accident (CVA) is controversieel. In het verleden kon geen voordeel van invasieve heelkunde aangetoond worden. De laatste jaren zijn minimaal invasieve methoden onderwerp van intensief onderzoek. In deze thesis wordt een overzicht gegeven van de meest recente literatuur omtrent heelkundige behandeling van hemorrhagisch CVA. Methode: We zochten gerandomiseerde gecontroleerde studies (RCT’s) en systematic reviews van de laatste vijf jaar in Cochrane Library, PubMed en Trip Database. De zoekactie leverde elf relevante artikels op. Resultaten: In de behandeling van intracerebrale bloedingen bleek minimaal invasieve heelkunde in de geïncludeerde studies niet gepaard te gaan met een hogere mortaliteit of morbiditeit dan conservatieve therapie. De studies konden geen overtuigende verbetering in functionele outcome aantonen. Ook minimaal invasieve chirurgie gecombineerd met toediening van alteplase bleek veilig, maar ook kon geen verbetering van functionaliteit aangetoond worden (p=0,33). Wel had minimaal invasieve heelkunde een significant betere kans op goed herstel in vergelijking met conventionele craniotomie (OR 2,27 [95% CI = 1,34 – 3,83]). In de behandeling van intraventriculaire bloedingen blijkt trombolyse niet superieur aan ventriculo-externe drainage. Conclusie: Minimaal invasieve heelkunde is veilig en superieur ten opzichte van conventionele craniotomie. In de vergelijking met conservatieve therapie is de literatuur tegenstrijdig. De meest recente grote studies tonen globaal geen significante meerwaarde. In de toekomst zijn meer grote prospectieve RCT’s nodig om duidelijke aanbevelingen te kunnen geven in specifieke patiëntengroepen.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

Background: Post-stroke depression (PSD) occurs in almost one-third of stroke survivors. Despite its high prevalence, it is still underdiagnosed and undertreated. In this retrospective, observational study, we explored the incidence of depressive symptoms in patients with acute stroke, examined the clinical characteristics and differences between patients with and without depressive symptoms, identified predictors for the development of depressive symptoms and assessed the effect of depressive symptoms on functional outcome. Methods: Data of all adult patients with stroke hospitalized at the stroke unit of the Leuven University Hospital (Belgium) from 7 December 2018 up to and including 29 December 2021 in whom a baseline Patient Health Questionnaire (PHQ)-2 was performed, were prospectively collected. Screening for depressive symptoms occurring up to two weeks prior to hospital admission or during hospitalization was performed using the PHQ-2 and -9. Functional outcome on day 90 was measured by the modified Rankin Scale (mRS). Results: From a total of 1356 patients hospitalized with stroke during the study period, we included 965 patients. Depressive symptoms were present in 54 patients (5.6%). Patients with depressive symptoms were younger, more likely to smoke, had a longer length of hospital stay and were less likely discharged to home compared to the non-depressive group. Predictors for the development of depressive symptoms during hospitalization were length of hospital stay and smoking status. We found an association between depressive symptoms and worse functional outcome in univariable analysis, which was no longer present in multivariable analysis after adjustment for relevant covariables (common odds ratio = 0.612, 95% confidence interval [0.303; 1.237], p 0.171). Conclusion: In this study, smoking and hospitalization length were associated with having depressive symptoms prior to or during hospitalization for acute stroke. After adjustment for relevant covariables, the presence of depressive symptoms was not associated with worse functional outcome at 90 days after stroke.

Choose an application

• Reference Manager
• EndNote
• RefWorks (Direct export to RefWorks)

After a stroke, about one third of the patients is faced with aphasia, a language disorder affecting speech comprehension and production. Persons with aphasia show very heterogeneous symptoms and vary in the degree to which each level of the speech processing chain, spectrotemporal, phonological or semantic processing, is affected. Although a precise diagnosis is vital for targeted intervention, behavioral testing can be very challenging due to communication problems as well as potential co-morbid cognitive problems. The aim of this project is to decode brain signal from EEG measures while patients listen to natural speech signals, that is a 30-minute-long story. We suggest to (1) detect aphasia with EEG, (2) determine in which processing stages resides the locus of the language disorder and (3) cluster patients with similar profiles and link them to behavioural results. Neural coding of the brain signals might improve the characterization of the language problems in stroke patients with aphasia, above and beyond behavioral measures.