A chronic subdural hematoma (CSDH) is an intracranial bleeding between the outer two meninges of the brain due to rupture of cerebral veins or an inflammatory response in the subdural space.... Show moreA chronic subdural hematoma (CSDH) is an intracranial bleeding between the outer two meninges of the brain due to rupture of cerebral veins or an inflammatory response in the subdural space. Elderly patients using anti-thrombotic therapy are at higher risk for hematoma development. A rise in CSDH incidence is expected because of the aging population and increase in anti-thrombotic therapy use due to cardiovascular disease. To date, no treatment guideline exists regarding optimal CSDH treatment. Surgery with subdural drainage is the mainstay treatment. However, due to relevant surgical complications, a recurrence risk up to 30% and increased mortality in this vulnerable patient population, corticosteroid therapy is being administered as an alternative or adjuvant treatment modality.In this thesis we have shown that surgical treatment results in significantly better treatment outcome than medicinal approach by the corticosteroid dexamethasone in a retrospective study (chapter 2) as well as in a randomized controlled trial (chapter 3 and 4). Furthermore, we revealed radiological markers that are of prognostic value to predict treatment outcome after surgery (chapter 5) and dexamethasone therapy (chapter 6) in symptomatic CSDH patients. Show less
Decompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity... Show moreDecompressive craniectomy (DC) in traumatic brain injury (TBI) has been suggested to influence cerebrovascular reactivity. We aimed to determine if the statistical properties of vascular reactivity metrics and slow-wave relationships were impacted after DC, as such information would allow us to comment on whether vascular reactivity monitoring remains reliable after craniectomy. Using the CENTER-TBI High Resolution Intensive Care Unit (ICU) Sub-Study cohort, we selected those secondary DC patients with high-frequency physiological data for both at least 24 h pre-DC, and more than 48 h post-DC. Data for all physiology measures were separated into the 24 h pre-DC, the first 48 h post-DC, and beyond 48 h post-DC. We produced slow-wave data sheets for intracranial pressure (ICP) and mean arterial pressure (MAP) per patient. We also derived a Pressure Reactivity Index (PRx) as a continuous cerebrovascular reactivity metric updated every minute. The time-series behavior of the PRx was modeled for each time period per patient. Finally, the relationship between ICP and MAP during these three time periods was assessed using time-series vector autoregressive integrative moving average (VARIMA) models, impulse response function (IRF) plots, and Granger causality testing. Ten patients were included in this study. Mean PRx and proportion of time above PRx thresholds were not affected by craniectomy. Similarly, PRx time-series structure was not affected by DC, when assessed in each individual patient. This was confirmed with Granger causality testing, and VARIMA IRF plotting for the MAP/ICP slow-wave relationship. PRx metrics and statistical time-series behavior appear not to be substantially influenced by DC. Similarly, there is little change in the relationship between slow waves of ICP and MAP before and after DC. This may suggest that cerebrovascular reactivity monitoring in the setting of DC may still provide valuable information regarding autoregulation. Show less
Depauw, P.R.A.M.; Groen, R.J.M.; Loon, J. van; Peul, W.C.; Malbrain, M.L.N.G.; Waele, J.J. de 2019
This thesis describes clinical, cytological, immunological and pharmacological aspects of acute childhood leukaemia and allogeneic stem cell transplantation(SCT), with the emphasis on the analysis... Show moreThis thesis describes clinical, cytological, immunological and pharmacological aspects of acute childhood leukaemia and allogeneic stem cell transplantation(SCT), with the emphasis on the analysis of potential improvements in risk stratification and possible treatment adaptation, in order to decrease relapse frequency and disease-related death. Firstly, to study the role of chemokine receptor/ligand interactions in the context of extramedullary leukaemia, we analyzed the homing receptor expression on leukemic blast cells in skin or intestine, peripheral blood and bone marrow of patients with T-ALL en AML, respectively. Secondly, the treatment results of 132 children, who received an allogeneic HLA-identical SCT for acute leukaemia was evaluated, showing the effect of biologically effective TBI dose on relapse risk. Thirdly, to optimize the use of Cyclosporin A(CsA) for adequate Graft-versus-host disease(GVHD) prophylaxis and to avoid drug toxicity, we investigated the pharmacokinetics of CsA in children after SCT, and showed that monitoring CsA exposure early after SCT may provide a tool to influence outcome. Finally, to gain a better understanding of the mechanism of chimerism induction of endothelial and epithelial cells following allogeneic SCT, the occurrence of chimerism in relation to the conditioning regimen, time interval after SCT and development of GVHD was studied. Show less
