Craniopharyngioma. Morbidity and Structural Changes in the Brain

Abstract: Hypothalamus (HT) is a brain structure which serves as a coordination center for several vital body functions. Craniopharyngioma (CP) is a pituitary tumor with high morbidity, primarily due to HT lesion. Among important consequences of CP are cognitive dysfunction and intractable weight gain due to HT obesity, resulting in high cardiovascular (CV) risk. A better understanding of the structural brain damage due to the tumor growth and/or its treatment, is a prerequisite for improved treatment and follow-up care of patients with CP. The focus of this thesis is to explore structural brain alterations and whether these may be associated with a) cognitive dysfunction b) metabolism. We begin by analyzing which cognitive domains are affected (paper I). We proceed to apply diffusion tensor imaging, a new technique in the field of magnetic resonance imaging to analyse the integrity of white matter (WM) neural pathways, as well as the HT (paper II-III). In addition, hippocampal volume was measured (paper II). The HT volume was explored in relation to anthropometric features and neuropeptides important in obesity. Postoperative risk stratification based on HT volume is proposed as a tool for improved postoperative follow-up care (paper IV). Finally, we analyse brain white matter lesions (WML) caused by chronic microvasculature hypoperfusion which may serve as a marker of increased risk for CV diseases and stroke (paper V). Our most important findings are that CP patients have impaired memory, disturbed attention and processing speed. WM alterations in the uncinate fasciculus are associated with worse general knowledge. The strongest correlation was found between visual memory and WM alterations in the cingulum. A smaller hippocampus, as well as WM alterations in the hippocampus, are associated with worse general knowledge. A decrease in HT volume is associated with increased fat mass and leptin among patients and we present a new method which may be valuable for postoperative risk assessment. CP patients have a significant increase in total WML volume which is associated with HT volume and cranial radiotherapy. In conclusion, there is an association between cognitive dysfunction and WM alterations among patients with CP. HT volume may serve as a tool for postoperative risk assessment. WML may be valuable for identification of high-risk CP patients providing an opportunity for early preventive treatment of CV diseases and stroke.