The cerebral circulation in preeclampsia : abnormalities in autoregulation and perfusion

Background: Eclampsia continues to be a major cause of maternal death. Abnormal cerebral blood flow and autoregulation may play an important role in the causation. Doppler ultrasound now allows assessment of the pathophysiology of preeclampsia, and the mechanisms of action of drugs used to treat it.

Objectives: The objectives of this thesis were to: (1) define normal ranges for middle cerebral artery velocity, resistance indices, and perfusion pressure in pregnancy, (2) validate a non- invasive method for the measurement of cerebral perfusion pressure (CPP), (3) evaluate cerebral arterial resistance in the middle cerebral artery (MCA) distribution in preeclampsia, (4) contrast CPP in mild and severe preeclampsia, (5) research the hemodynamics of headache in preeclampsia, and (6) compare the effects of magnesium sulfate (MgSO4) and nimodipine on CPP in preeclampsia.

Materials and Methods: Normal pregnant and preeclamptic patients were recruited. Vital signs, epidural pressure, and the velocities in cerebral and orbital arteries were measured. Indices of resistance and cerebral perfusion pressure (CPP) were calculated for both groups and compared. Preeclamptic women were studied before and after they had been randomly assigned to receive MgSO4, or nimodipine. Appropriate parametric and non-parametric tests were used in the analysis of the data. A two-tailed p<0.05 denoted statistical significance.

Major Findings and Conclusions: 1. Normal pregnancy is associated with a decrease in systolic and mean velocity, no change in the diastolic velocity, a decrease in resistance indices, and an increase in MCA CPP. 2. CPP may be reliably measured in the MCA using a simple Doppler and non-invasive blood pressure technique. 3. Preeclampsia preferentially effects the MCA and disturbs autoregulation in this artery. 4. More than 50% of women with preeclampsia have a normal CPP. In mild preeclampsia, the CPP may be low or high, but in severe preeclampsia, if abnormal, CPP is always high. 5. Preeclamptics with headache more likely to have abnormal CPP than those without, and when headache is present it is more commonly associated with high CPP than low. 6. Nimodipine increases CPP, while MgSO4, causes a decrease in CPP, within 3 0 minutes after administration.

Significance: Normal ranges for velocity, resistance and CPP have been defined for pregnancy. A new technique for measuring MCA CPP in pregnant women has been validated and may prove useful in research in this condition. The potential for overperfusion of the brain due to MCA autoregulation abnormalities should now be considered when treating preeclamptics. The use of CPP measurements may help in the management of women at high risk for seizure. Efforts should perhaps be directed at determining the CPP in selected women to help tailor therapy. Since headache is associated with abnormally high CPP, efforts to lower CPP should be considered when headache develops in a preeclamptic woman. Drugs that increase CPP are probably best avoided in patients with preeclampsia (especially those with headache) because of their potential for worsening hypertensive encephalopathy. They should be reserved for use in known cases of low CPP.

List of scientific papers

I. Belfort MA, Tooke-Miller C, Allen JC Jr, Saade GR, Dildy GA, Grunewald C, Nisell H, Herd JA (2001). "Changes in flow velocity, resistance indices, and cerebral perfusion pressure in the maternal middle cerebral artery distribution during normal pregnancy" Acta Obstet Gynecol Scand 80(2):: 104-12
https://pubmed.ncbi.nlm.nih.gov/11167203

II. Belfort MA, Tooke-Miller C, Varner M, Saade G, Grunewald C, Nisell H, Herd JA (2000). "Evaluation of a noninvasive transcranial Doppler and blood pressure-based method for the assessment of cerebral perfusion pressure in pregnant women" Hypertens Pregnancy 19(3): 331-40
https://pubmed.ncbi.nlm.nih.gov/11118407

III. Belfort MA, Saade GR, Grunewald C, Dildy GA, Varner MA, Nisell H (1999). "Effects of blood pressure on orbital and middle cerebral artery resistances in healthy pregnant women and women with preeclampsia" Am J Obstet Gynecol 180(3 Pt 1): 601-7
https://pubmed.ncbi.nlm.nih.gov/10076135

IV. Belfort MA, Grunewald C, Saade GR, Varner M, Nisell H (1999). "Preeclampsia may cause both overperfusion and underperfusion of the brain: a cerebral perfusion based model" Acta Obstet Gynecol Scand 78(7):: 586-91
https://pubmed.ncbi.nlm.nih.gov/10422904

V. Belfort MA, Saade GR, Grunewald C, Dildy GA, Abedejos P, Herd JA, Nisell H (1999). "Association of cerebral perfusion pressure with headache in women with pre-eclampsia" Br J Obstet Gynaecol 106(8): 814-21
https://pubmed.ncbi.nlm.nih.gov/10453832

VI. Belfort MA, Saade GR, Yared M, Grunewald C, Herd JA, Varner MA, Nisell H (1999). "Change in estimated cerebral perfusion pressure after treatment with nimodipine or magnesium sulfate in patients with preeclampsia" Am J Obstet Gynecol 181(2): 402-7
https://pubmed.ncbi.nlm.nih.gov/10454691