Detection of Epileptiform Activity in Severe Preeclampsia
Detection of Epileptiform Activity in Severe Preeclampsia
The primary aim of this pilot study is to prospectively quantify epileptiform activity in a
 cohort of preeclamptic patients before and after intravenous magnesium administration.

 Secondary aims will be the exploration of a potential association between epileptiform
 activity and the sFlt-1:PIGF ratio, as well as a correlation to clinical signs of
 preeclampsia.

 A positive finding may aid obstetricians to detect an increased convulsive risk by performing
 a simplified EEG early in the diagnostic path of preeclampsia. If confirmed in a larger trial
 positive correlations of an increased sFlt-1:PIGF ratio with epileptiform activity might be a
 risk marker for early severe preeclampsia, guiding obstetricians into clinical
 decision-making in regard to an increased maternal risk of eclampsia.
Preeclampsia constitutes a heterogeneous multisystemic disorder defined by the new onset of
 hypertension and proteinuria after 20 weeks of gestation.1 The incidence of preeclampsia in
 Switzerland is estimated at 2.31 % of pregnancies (95% CI 1.62-3.28%), about 1'911 cases/year
 can be expected to occur on the national level. Preeclampsia and eclampsia are considered a
 continuum in the hypertensive disorders of pregnancy. When convulsions or coma occur in
 addition to hypertension the condition is referred to as eclampsia. Up to 2-3% of severely
 preeclamptic women will have eclampsia,4 with a consecutive mortality rated between 0-14%.5
 The diagnosis of preeclampsia is challenging, because of clinical heterogenity, especially at
 early stages. Until recently no routine laboratory test or biological marker other than
 presenting clinical symptoms such as severe headache or arterial hypertension, decreased
 plasmatic thrombocyte count and proteinuria were available for diagnostic purposes.

 The only curative treatment of severe preeclampsia and eclampsia consists of delivery of
 fetus and placenta. Since the 2002 Magpie trial, the mainstay of eclampsia prevention in
 severely preeclamptic patients relies on the prophylactic use of intravenous magnesium,
 either when prompt delivery can be performed, or if it has to be delayed for fetal reasons.
 Obviously, eclampsia prevention is critical, considering that eclampsia onset can occur pre,
 intra, or postpartum. Hereby the prophylactic magnesium treatment is mostly maintained
 throughout a period of several days before and after delivery of the fetus and placenta, as
 up today there is no reliable clinical or diagnostic approach to predict the risk of
 eclamptic seizures.

 The actual gold standard in high-risk maternities is to assess clinical symptoms as described
 above and perform newer laboratory essays, in order to estimate the parturient's risk for
 preeclamptic complications. Insofar changes in serum levels of fms-like tyrosine kinase-1
 (sFlt-1) and placental growth factor (PGIF) were lately revealed and have been currently
 approved as diagnostic aid in preeclampsia. Circulating maternal serum levels of sFlt-1 are
 increased, and PGIF are decreased in preeclampsia. As an antagonist of PGIF and vascular
 endothelial growth factor, sFlt-1 causes vasoconstriction and endothelial damage. Noteworthy
 a sFlt-1:PIGF ratio lower than 38 can be used as to predict a short-term absence of
 preeclampsia in women with suspect clinical symptoms.

 Interestingly novel knowledge points to a strong link in between plasmatic steroid hormones
 and epilepsy, with strong animal data pointing towards a higher epileptogenic potential in
 high estrogenic states; whereas androgens, namely progesterone seem to induce a protective
 state through agonism on extrajunctional GABAA receptors.

 EEG slopes are good markers for epileptiform activity. EEG changes have been reported in
 eclampsia and in severe preeclampsia, with differences also reported between severe
 preeclampsia and eclampsia.Recently, slow waves most frequently localized in the occipital
 lobe, as well as spike discharges in EEG, were reported as warning signs of deterioration of
 brain function in preeclampsia or eclampsia. Neither have electroencephalic correlates of
 sFlt-1, PGIF or hormonal states been investigated in preeclampsia. EEG is not in routine use
 for convulsive risk assessment in maternity wards, when preeclampsia screening is performed.
 One of the reasons might be that performing EEGs is time consuming and involves significant
 human resources for urgent EEG analysis. These resources might be lacking even in tertiary
 hospitals. Novel reliable, noninvasive and technically easy to perform simplified EEG methods
 have become available, these are especially in use during anesthesia for detection of
 clinically silent epileptic potentials.
Inclusion Criteria:

 1. Confirmed pregnancy > 30 weeks of gestation

 2. Singleton or multiple pregnancies

 3. Admission in maternity of the Women's hospital with clinically suspected signs of
 severe preeclampsia:

 -  Systolic blood pressure >140 mmHg or diastolic pressure > 90 mmHg and

 -  Proteinuria > 0.3 grams in a 24-hour urine or protein:creatinine ratio >0.3 or

 -  Signs of end-organ dysfunction (platelet count < 100'000G/l, serum creatinine
 >110 mg/l, or doubling of the serum creatinine, elevated serum transaminases to
 twice normal concentration)

 Exclusion Criteria:

 1. Lack of patient's informed consent

 2. Active labor

 3. Eclampsia

 4. Hypertensive crisis as defined by Systolic blood pressure > 210 mmHg or diastolic
 pressure > 120 mmHg

 5. Known epilepsy

 6. Posterior reversible encephalopathy syndrome

 7. Antiepileptic medication (except magnesium sulfate)

 8. Reported or admitted medication or substance abuse (street drugs, opiates,
 benzodiazepines, alcohol)

 9. Known neurologic condition with previously pathologic diagnostic imaging or EEG

 10. Severe fetal malformations (abdominal: gastroschisis & omphalocele, tracheoesophageal
 fistula, cerebral: brain malformations included in the category of cephalic disorders,
 pulmonary: lung hypoplasia, cardiac: congenital heart disease)

 11. Preceding rupture of membranes

 12. Non-German and non-French speaking parturient