The main objective of this thesis is to compare bony decompression with implantation of interspinous process devices (IPDs) in patients with intermittent neurogenic claudication (INC) caused by... Show moreThe main objective of this thesis is to compare bony decompression with implantation of interspinous process devices (IPDs) in patients with intermittent neurogenic claudication (INC) caused by lumbar spinal stenosis (LSS). A national survey among Dutch spine surgeons is presented about the usual care of patients with intermittent neurogenic claudication caused by lumbar spinal stenosis. Surgeons' expectations of different treatment options are presented. The existing evidence on interspinous implant surgery will be systematically reviewed. Results of treatment with IPDs are compared with other (conservative) treatment options. The Foraminal Enlargement Lumbar Interspinosus distraXion (FELIX) trial is described. This double-blind, multicenter, randomized (cost)effectiveness study was designed to answer the question whether treatment with IPDs would be more (cost) effective compared with conventional bony decompression. Short-term results (eight weeks), long-term results (one and two year) and results in different subgroups are described in this thesis. The analysis based on total direct and indirect costs of both procedures (treatment with IPD and bony decompression) are also presented. INC suitable for surgical treatment. The compression on MR images was evaluated and correlated with baseline complaints and long-term clinical outcome. Show less
Cardiovascular risk assessment in patients with diabetes mellitus (DM) remains challenging. Risk scores to predict cardiovascular risk are widely used, but are developed in the general population... Show moreCardiovascular risk assessment in patients with diabetes mellitus (DM) remains challenging. Risk scores to predict cardiovascular risk are widely used, but are developed in the general population and tend to underestimate the cardiovascular risk of DM patients. Risk scores developed in diabetic populations to estimate cardiovascular risk have demonstrated good calibration and discriminations indices. However, external validation is still needed. A recent meta-analysis showed that the predictive ability of these scores developed in diabetic populations is not superior to those scores developed in general population. Accordingly, the additional use of other biomarkers or imaging tools seems a good alternative to better risk stratify diabetic patients. This thesis evaluates the application and performance of non-invasive cardiac imaging tests for cardiovascular risk assessment and management of DM patients. Identification of new markers of CAD derived from non-invasive cardiac imaging might result in a broader applicability of cardiovascular risk assessment. Non-invasive cardiac imaging tests might evaluate target organ damage as well as the presence, severity and extent of subclinical atherosclerosis preceding overt clinical CAD. Thus, high-risk patients for CAD can be identified and further decision making of each DM patient can be tailored in order to improve the clinical outcomes at long-term follow-up Show less
The general objective of this thesis was to investigate new (quantitative) MR techniques and MR markers in the light of both AD and cerebral aging. The quantitative MR techniques that we used were... Show moreThe general objective of this thesis was to investigate new (quantitative) MR techniques and MR markers in the light of both AD and cerebral aging. The quantitative MR techniques that we used were MTI, tCBF and WSS measurements. The new markers we studied were cerebral microbleeds and iron accumulation in the basal ganglia. In chapter 2 we investigated whether MTI changes could be detected in the GM, WM or both in patients suffering from MCI or AD. Using MTI we found evidence for structural brain changes in both GM and WM of patients with MCI and AD. Furthermore, these MTI changes were related to cognitive impairment as expressed by the mini mental state examination (MMSE) score. These findings imply that cerebral changes can be detected in both GM and WM even before patients are clinically demented. The finding of MTI changes in the GM might relate to classical AD type pathology, whereas WM MTI changes could indicate concomitant vascular pathology. The findings in chapter 2 raised the question of how the MTI changes found in this study are distributed over the GM and WM. This was investigated in chapter 3. In this study we showed that brain damage, as detected by MTI, is widespread over the lobes in both AD and MCI patients whereas GM damage is more focally present in the temporal and frontal lobe of MCI patients. These findings are compatible with the knowledge that GM damage originates from the temporal lobe in AD. This interpretation is further supported by the observed independent association between temporal GM peak height and cognitive decline. MTI changes were found in all four lobes of the MCI patients investigated in this study and show the involvement of a diffuse process affecting the WM even before patients are clinically demented, a finding potentially explained by the presence of diffuse vascular pathology. Chapter 4 shows that the tCBF is strongly associated with parenchymal volume rather than age and, although much weaker, with the severity of WMHs. Although the association between tCBF and parenchyma volume seems straightforward, this finding has important implications for future studies. Volume flow measurements should be corrected for parenchymal volume ratherthan age in all future studies in which flow measurements are being used as a diagnostic tool. In addition, studies including elderly patients or patients with a pathological increase of WMHs, such as diabetic type II subjects, should also correct their tCBF measurements for WMH volumes. Chapter 5 shows that hemodynamic conditions of the carotid and basilar arteries, as expressed in lower WSS parameters, are worse in both MCI and AD compared to controls. In addition, the WSS parameters were found to correlate strongly with cognition. Again, this study is additional evidence for an important role of vascular pathology in the development of AD. In chapter 6, we found a high prevalence of microbleeds in a population of patients suffering from vascular disease or at high risk of developing this condition. Age, hypertension and WMH were the most important risk factors for microbleeds, especially when located in the cortico-subcortical junction and basal ganglia. Regarding the associations between the presence and location of microbleeds on the one hand and parameters of cognitive functioning on the other, chapter 7 shows that microbleeds located infratentorially are associated with impaired cognitive functioning in the aging population with increased vascular risk factors. This suggests that in elderly individuals microbleeds in the posterior fossa should be considered a sign of small vessel disease with potential functional consequences. The semi-quantative scale for scoring basal ganglia hypo-intensity on T2*- weighted imaging presented in chapter 8 was associated with markers of neurodegeneration. This study showed that low signal intensity of the caudate nucleus T2*-weighted MR is a frequent finding which is associated with more cerebral atrophy, a higher load of WMH and a higher load of invisible changes in both cortical GM and NAWM non-demented elderly. Furthermore, hypo- intensity limited to the globus pallidus and putamen was not associated with any of these parameters of neurodegeneration. In chapter 9 we present a method for automated detection and classification of hypo-intense regions on T2-weighted MR images of the basal ganglia. In this chapter we not only show an association between basal ganglia hypo-intensity and cardiovascular risk factors but also with measures of cognitive functioning. From this we conclude that hypo-intensity of the basal ganglia on T2-weighted MR is not only a radiological finding accompanying cerebral aging but also an independent marker of neurodegeneration. Show less
