Preeclampsia and the Brain : Epidemiological and Magnetic Resonance Studies

Sammanfattning: Preeclampsia is a pregnancy specific syndrome that causes substantial maternal and fetal morbidity and mortality. One major contributor to maternal deaths is eclampsia, i.e. when seizures arise in the context of preeclampsia. The pathophysiology of eclampsia is still incompletely chartered and the long-term cerebral consequences of preeclampsia are also largely unknown.This thesis consists of a register based cohort study (n=3232, study I), and a cross-sectional neuroimaging study of pregnant women with and without preeclampsia (n=78, studies II-IV).In paper I, we compared the incidence of dementia and cardiovascular disease (CVD) between women ≥65 years with a self-reported history of hypertensive pregnancy, and women with a normotensive pregnancy. No difference was found regarding dementia, but an increased risk of CVD persisted among these elderly women.In paper II, we used phosphorus magnetic resonance spectroscopy to measure cerebral magnesium levels (Mg2+). We found lower levels of Mg2+ in women with preeclampsia than in women with normal pregnancy and non-pregnant women. Further, which was novel, we showed that lower cerebral Mg2+levels correlated with visual disturbances. The findings are interesting, since magnesium sulfate is the most effective treatment and prophylaxis for eclampsia, but with a largely unknown mechanism of action.In paper III, we measured cerebral organic osmolytes with proton magnetic resonance spectroscopy and found lower levels of osmolytes in pregnancy. Cerebral osmolytes were positively correlated with a decreased plasma osmolality, indicating that there is a joint biological mechanism. The only osmolyte that differed between women with preeclampsia and healthy pregnant women was glutamate. Glutamate is an excitatory neurotransmitter, which also functions as an osmolyte. Thus, lower cerebral glutamate levels could have implications on the pathophysiology of seizures.In paper IV, cerebral perfusion and edema were assessed with magnetic resonance imaging using intravoxel incoherent motion technique. A reduced perfusion fraction was found in a part of the basal ganglia in women with preeclampsia. No difference in edema was detected.Our findings indicate Mg2+ metabolism, plasma hypoosmolality and possibly cerebral hypoperfusion to be involved in the pathophysiology of cerebral affection in preeclampsia.