Signs of neuroaxonal injury in preeclampsia—A case control study

Abstract

Background Cerebral injury is a common cause of maternal mortality due to preeclampsia and is challenging to predict and diagnose. In addition, there are associations between previous preeclampsia and stroke, dementia and epilepsy later in life. The cerebral biomarkers S100B, neuron specific enolase, (NSE), tau protein and neurofilament light chain (NfL) have proven useful as predictors and diagnostic tools in other neurological disorders. This case-control study sought to determine whether cerebral biomarkers were increased in cerebrospinal fluid (CSF) as a marker of cerebral origin and potential cerebral injury in preeclampsia and if concentrations in CSF correlated to concentrations in plasma. Methods CSF and blood at delivery from 15 women with preeclampsia and 15 women with normal pregnancies were analysed for the cerebral biomarkers S100B, NSE, tau protein and NfL by Simoa and ELISA based methods. MRI brain was performed after delivery and for women with preeclampsia also at six months postpartum. Results Women with preeclampsia demonstrated increased CSF- and plasma concentrations of NfL and these concentrations correlated to each other. CSF concentrations of NSE and tau were decreased in preeclampsia and there were no differences in plasma concentrations of NSE and tau between groups. For S100B, serum concentrations in preeclampsia were increased but there was no difference in CSF concentrations of S100B between women with preeclampsia and normal pregnancy. Conclusion NfL emerges as a promising circulating cerebral biomarker in preeclampsia and increased CSF concentrations point to a neuroaxonal injury in preeclampsia, even in the absence of clinically evident neurological complications.

Cerebral Biomarkers and Blood-Brain Barrier Integrity in Preeclampsia

“…Recently published results from our research group reported increased concentrations of NfL in both plasma and CSF in women with preeclampsia compared with normotensive pregnant women. In addition, there was a strong correlation between concentrations of NfL in plasma and CSF [ 42 ]. Previous studies of women with preeclampsia have not been able to establish whether a BBB impairment exists in these women or not [ 43 ]; however, human studies are few on this subject.…”

Evidence of Neuroinflammation and Blood–Brain Barrier Disruption in Women with Preeclampsia and Eclampsia

“…In one study that had previously investigated the CSF/plasma albumin ratio, 15 women with preeclampsia and 15 women with normotensive pregnancies were included. There were no women with eclampsia in this study [ 15 ]. One woman in the preeclampsia group had HELLP syndrome but none had eclampsia or other severe end organ complications.…”

“…In the normotensive group, the CSF/plasma albumin ratio was 2.73, similar to our findings of 3.1. Women with preeclampsia had a median CSF/plasma albumin ratio of 3.02 [ 15 ]. In our study, the median CSF/plasma albumin ratio in women with preeclampsia was 5.2.…”

“…In addition, the CSF/plasma albumin ratio was increased in preeclampsia as a measurement of blood–brain barrier impairment [ 10 , 12 , 13 , 14 ]. So far, there has been no evidence from pregnant women with preeclampsia to support this finding, with only one study having found increased levels of interleukins in CSF in preeclampsia, although other studies have not [ 15 , 16 , 17 , 18 ]. To our knowledge, no studies have assessed neuroinflammation and the blood–brain barrier in women with eclampsia.…”

Potential role of neurofilament in COVID-19 and preeclampsia

“… 14 In another study, women with preeclampsia without clinically detectable neurological complications had increased CSF and plasma concentrations of NFL compared to women with normotensive pregnancies. 15 However, scant information is currently available regarding the origin, importance, and role of sNFL, and there are no reliable blood tests to predict eclampsia- or preeclampsia-induced cerebral edema. Furthermore, few data exist on sNFL in term and preterm infants.…”