Aspects of migraine and patent foramen ovale in ischemic stroke

by Maria Lantz

Institution: Karolinska Institute
Year: 2017
Posted: 02/01/2018
Record ID: 2155100
Full text PDF: http://hdl.handle.net/10616/45625


Stroke is one of the main causes of death and disability worldwide, and only in Sweden approximately 25 000 individuals suffer from stroke each year. This thesis focuses on two common conditions; migraine and patent foramen ovale (PFO) and their role in stroke.Migraine is a common primary headache disorder, affecting approximately 11-13 % of the population with a 3:1 female preponderance. One third of the patients have an initial aura of neurological symptoms before the headache, and clinically migraine can be divided into migraine with and without aura. The pathophysiological mechanisms are highly complex, and involve cortical spreading depression (CSD) as the substrate for migraine aura, and activation of the trigeminovascular system causing the headache.PFO is an inborn anomaly, a remnant from the fetal circulation, that is prevalent in approximately 25 % of the population. PFO enables shunting of venous blood to the arterial circulation, bypassing the pulmonary system and enables paradoxial embolization. PFO is associated with ischemic stroke, as well as migraine with aura. The reason for the latter is unknown, but may relate to micro-embolisms through a PFO triggering migraine attacks.For decades, migraine has been suggested as a risk factor for stroke and cardiovascular disease. The risk seems to be mostly related to migraine with aura, female gender and young age. The reasons for this are still unknown and probably multifactorial. Different theories involve increased prevalence of cardiovascular risk factors among migraineurs, co-existence of other co-morbid conditions increasing the risk for stroke (i.e. PFO and cervical artery dissection), and association to endothelial dysfunction with subsequent hypercoagulability and decreased vascular reactivity. Migraine with aura may also be associated with a phenotype, leading to an increased susceptibility for CSD, and an increased sensitivity to cerebral ischemia. This thesis involves four different projects concerning PFO and migraine in relation to stroke. The projects are performed in stroke populations (Study I-III) and in a population-based twin sample (Study IV).In Study I, patients with ischemic stroke investigated with transesophageal echocardiography were included (N=117), and dichotomized depending on the co-existence of a PFO. The prevalence of PFO was 11.9 %. Patients were analyzed regarding cardiovascular risk factors and allele frequency of 100 different genetic markers, previously associated with cerebrovascular disease. Four genetic markers, located in the Prothrombin-, Selectin E- and Apolipoprotein C III- genes, were significantly associated with PFO. The strongest association was for Prothrombin 20210 G/A (p= 0.0049), which is a marker associated with increased risk of venous thromboembolism. There were no differences regarding risk factors in the two groups.In Study II, patients with a diagnosis of TIA, ischemic or hemorrhagic stroke, admitted to the stroke ward during a six-month period, were included