Arjen Lindenholz

191 General Discussion 9 First , intracranial vessel wall lesions as seen at 7T MRI in patients with previous ischemic stroke or transient ischemic attack (TIA) are associated with several well-known cardiovascular risk factors, such as increasing age, hypertension and diabetes mellitus ( Chapter 5 ), suggesting that these lesions may indeed represent mild to moderate stages of intracranial atherosclerosis. These findings are comparable with those of a larger community-based 3T vessel wall MRI study – although the study populations of these studies differed – and similar results were seen in a 7T MRI study among patients with a history of (mainly non-cerebral) vascular disease. 37-39 Interestingly, in all three studies no association was found between vessel wall lesions and smoking, while varying associations were seen with the presence of hyperlipidemia. Possible explanations may be the relatively low number of participants, a difference in association between high-risk and low-risk cardiovascular status of participants, different ethnic backgrounds of participants, or a difference in risk factors between extracranial and intracranial arteries, although the latter is not supported by comparative studies. 38,40-43 Finally, due to the arbitrarily chosen cutoff value of vessel wall thickening and lack of histopathological validation, some detected vessel wall lesions may be less clinically relevant or represent normal fluctuations of vessel wall thickness, thereby underestimation the true effect. Nevertheless, in all three studies – with population-based, cardiovascular compromised and symptomatic participants – clear associations were found, suggesting a true relationship between intracranial vessel wall lesions and cardiovascular risk factors. Second , these same intracranial vessel wall lesions were associated with cerebral parenchymal (vascular) damage; more specifically, with the presence of any type of infarct and of periventricular white matter hyperintensities ( Chapter 6 ). Interestingly, the types of parenchymal damage with which an association was found, are generally linked to small vessel disease (SVD), not to large vessel atherosclerosis. These findings not only suggest that vessel wall lesions could be clinically relevant, but also implies a relationship between large vessel wall changes and (manifestations of) small vessel disease and/or that these vessel wall changes occur simultaneously . Currently, it remains to be further elucidated whether and in which way these associations exist. Some studies have proposed connecting mechanisms, such as the ‘parent artery atheroma theory’ in which atherosclerotic plaques in parent arteries cause an occlusion at the orifices of smaller branching arteries resulting in parenchymal damage, while others describe large artery disease and SVD as different entities. 44-47 Direct comparison of these studies is often difficult because of differences in used definitions and imaging methods for large artery disease, such as total lesion burden (varying form early to end- stage atherosclerosis) or solely stenotic lesions, and SVD, with a variety of possible parenchymal manifestations. 48-52 Larger studies with more uniformmeasurements and outcomes may contribute to further understanding the potential relationship