Correlation between cognitive assessment scores and circulating cerebral biomarkers in women with pre-eclampsia and eclampsia

OBJECTIVES: The cerebral injury biomarkers neurofilament light chain (NfL) and tau and the glial activation biomarker glial fibrillary acidic protein (GFAP) may reflect neurological injury in pre-eclampsia. We assessed if there was a correlation between cognitive function assessment scores and plasma concentrations of these biomarkers in pre-eclampsia. STUDY DESIGN: Women with eclampsia, pre-eclampsia and normotensive pregnancies from the South African PROVE biobank were included. Blood samples were taken at inclusion. The Montreal Cognitive Assessment was performed after delivery at the time of discharge. The correlation between cognitive assessment scores and plasma concentrations of cerebral biomarkers was analysed using Spearman correlation adjusted for time from eclamptic seizure. MAIN OUTCOME MEASURES: We included 49 women with eclampsia, 16 women with pre-eclampsia complicated by pulmonary oedema, 22 women with pre-eclampsia without pulmonary oedema, HELLP or neurological complications and 18 women with normotensive pregnancies. RESULTS: There was a correlation between impaired cognitive function and increased plasma concentrations of NfL in women with eclampsia and women with pre-eclampsia and pulmonary oedema (r = -0.37, p = 0.009 and r = -0.56, p = 0.025 respectively). No correlation between impaired cognitive function and NfL in pre-eclampsia cases without pulmonary oedema, HELLP or neurological complications or normotensive pregnancies was found. No correlation with cognitive impairment was found in any groups for tau or GFAP. CONCLUSIONS: We found a correlation between impaired cognitive function assessment and plasma NfL concentrations in women with eclampsia and pre-eclampsia complicated by pulmonary oedema. These findings suggest that acute neuroaxonal injury may cause or contribute to cognitive impairment in these women

Cerebral biomarkers in neurological complications of preeclampsia

BACKGROUND AND OBJECTIVES: There are no tools to accurately predict who is at risk of developing neurological complications of preeclampsia and no objective methods to determine disease severity. We assessed whether plasma levels of the cerebral biomarkers neurofilament light (NfL), tau and glial fibrillary acidic protein (GFAP) could reflect disease severity in various phenotypes of preeclampsia and compared them to the angiogenic biomarkers soluble fms-like tyrosine kinase 1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng) . STUDY DESIGN: In this observational study, we included women from the South African PROVE biobank. Plasma samples taken at diagnosis (preeclampsia cases) or at admission for delivery (normotensive controls) were analyzed for concentrations of NfL, tau, GFAP, PlGF, sFlt-1 and sEng. Cerebrospinal fluid concentrations of inflammatory markers and albumin were analyzed in a subgroup of 15 women. Analyses were adjusted for gestational age, time from seizures and delivery to sampling, maternal age and parity. RESULTS: Compared to 28 normotensive pregnancies, 146 women with preeclampsia demonstrated 2.18-fold higher plasma concentrations of NfL (95% CI 1.64-2.88), 2.17-fold higher tau (1.49-3.16) and 2.77-fold higher GFAP (2.06-3.72). In total 72 women with neurological complications (eclampsia, cortical blindness and stroke) demonstrated increased plasma concentrations of tau (2.99-fold higher, 95% CI 1.92-4.65) and GFAP (3.22-fold higher, 95% CI 2.06-5.02) compared to women with preeclampsia without pulmonary edema, HELLP or neurological complications (n=31). Angiogenic markers were also higher but to a lesser extent. Women with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome (n=20) demonstrated increased plasma concentrations of NfL (1.64-fold higher, 95% CI 1.06-2.55), tau (4.44-fold higher, 95% CI 1.85-10.66) and GFAP (1.82-fold higher, 95% CI 1.32-2.50) compared to women with preeclampsia without pulmonary edema, HELLP or neurological complications . No difference was shown in angiogenic biomarkers. There was no difference between 23 women with preeclampsia complicated by pulmonary edema and women with preeclampsia without pulmonary edema, HELLP or neurological complications for any of the biomarkers. Plasma concentrations of tau and GFAP were increased in women with several neurological complications vs eclampsia only. CONCLUSIONS: Plasma NfL, GFAP and tau are candidate biomarkers for diagnosis and possibly prediction of cerebral complications of preeclampsia

PROVE-Pre-Eclampsia Obstetric Adverse Events:Establishment of a Biobank and Database for Pre-Eclampsia

Pre-eclampsia is a leading cause of maternal and perinatal morbidity and mortality. The burden of disease lies mainly in low-middle income countries. The aim of this project is to establish a pre-eclampsia biobank in South Africa to facilitate research in the field of pre-eclampsia with a focus on phenotyping severe disease.The approach of our biobank is to collect biological specimens, detailed clinical data, tests, and biophysical examinations, including magnetic resonance imaging (MRI) of the brain, MRI of the heart, transcranial Doppler, echocardiography, and cognitive function tests.Women diagnosed with pre-eclampsia and normotensive controls are enrolled in the biobank at admission to Tygerberg University Hospital (Cape Town, South Africa). Biological samples and clinical data are collected at inclusion/delivery and during the hospital stay. Special investigations as per above are performed in a subset of women. After two months, women are followed up by telephonic interviews. This project aims to establish a biobank and database for severe organ complications of pre-eclampsia in a low-middle income country where the incidence of pre-eclampsia with organ complications is high. The study integrates different methods to investigate pre-eclampsia, focusing on improved understanding of pathophysiology, prediction of organ complications, and potentially future drug evaluation and discovery

The Naval Postgraduate School secure archival storage system, Part II : Segment and process management implementation

The security kernel technology has provided the technical foundation for highly reliable protection of computerized information. However, the operating system implementations face two significant challenges: providing (1) adequate computational resources for applications tasks, and (2) a clean, straightforward structure whose correctness can be easily reviewed. This paper presents the experience on an ongoing security kernel implementation using the Advanced Micro Devices 4116 single-board computer based on the Z8002 microprocessor. The performance issues of process switching, domain changing, and multiprocessor bus contention are explicitly addressed. The strictly hierarchical (i.e., loop-free) structure provides a series of increasingly capable, separately usable operating system subsets. Security enforcement is structured in two layers: the basic kernel rigorously enforces a non-discretionary (viz., lattice model) policy, while an upper layer provides the access refinements for a discretionary policy. (Author)supported by grants from the Office of Naval Research, Project No. 427-001, monitored by Mr. Joel Trimble, and the Naval Postgraduate School Research Foundationhttp://archive.org/details/navalpostgraduat00coxlN000148lWRl003

Post-COVID-19 Impairment of the Senses of Smell, Taste, Hearing, and Balance

Background: Various symptoms have been associated with COVID-19, but little is known about the impacts of COVID-19 on the sensory system, risk factors, and the duration of symptoms. This study assesses olfactory, gustatory, hearing, and vestibular systems after COVID-19. Methods: This cross-sectional, single-center study involved 50 patients one to six months after COVID-19 and reports their patient records and the extent, onset, and duration of olfactory, gustatory, hearing, and balance disorders using questionnaires during and after COVID-19. Sensory symptoms were objectively studied using the following clinical tests after COVID-19 Sniffin’ Sticks, taste tests, tone/speech audiometry, and video head impulse test. Results: Post-COVID-19-patients were suffering from olfactory and gustatory impairment for up to six months. According to the Dizziness Handicap Inventory, balance disorders were less noticed: Overall, about 40% of the patients during COVID-19 and nearly all patients recovered within six months. After COVID-19, clinical tests revealed that 75% were suffering from hyposomnia/anosmia, and 20% of all patients reported mild hypogeusia for up to six months. Vestibular disorders and hearing impairment rarely/did not occur. Females were significantly more affected by sensory impairments than males. Conclusions: COVID-19 particularly caused olfactory and gustatory impairment; balance disorders were present too; vestibular and auditory symptoms were negligible

Correlation between cognitive assessment scores and circulating cerebral biomarkers in women with pre-eclampsia and eclampsia

Objectives: The cerebral injury biomarkers neurofilament light chain (NfL) and tau and the glial activation biomarker glial fibrillary acidic protein (GFAP) may reflect neurological injury in pre-eclampsia. We assessed if there was a correlation between cognitive function assessment scores and plasma concentrations of these biomarkers in pre-eclampsia. Study design: Women with eclampsia, pre-eclampsia and normotensive pregnancies from the South African PROVE biobank were included. Blood samples were taken at inclusion. The Montreal Cognitive Assessment was performed after delivery at the time of discharge. The correlation between cognitive assessment scores and plasma concentrations of cerebral biomarkers was analysed using Spearman correlation adjusted for time from eclamptic seizure. Main outcome measures: We included 49 women with eclampsia, 16 women with pre-eclampsia complicated by pulmonary oedema, 22 women with pre-eclampsia without pulmonary oedema, HELLP or neurological complications and 18 women with normotensive pregnancies. Results: There was a correlation between impaired cognitive function and increased plasma concentrations of NfL in women with eclampsia and women with pre-eclampsia and pulmonary oedema (r = -0.37, p = 0.009 and r = -0.56, p = 0.025 respectively). No correlation between impaired cognitive function and NfL in pre-eclampsia cases without pulmonary oedema, HELLP or neurological complications or normotensive pregnancies was found. No correlation with cognitive impairment was found in any groups for tau or GFAP. Conclusions: We found a correlation between impaired cognitive function assessment and plasma NfL concentrations in women with eclampsia and pre-eclampsia complicated by pulmonary oedema. These findings suggest that acute neuroaxonal injury may cause or contribute to cognitive impairment in these women

Cognitive impairment in preeclampsia complicated by eclampsia and pulmonary edema after delivery

Introduction We aimed to assess cognitive function in women with preeclampsia stratified by severity, before and after onset of disease. Material and methods Prospective study performed at a referral hospital in Cape Town, South Africa. Pregnant women between 20 and 42 weeks of gestation with eclampsia, pulmonary edema and preeclampsia without severe features, and a normotensive pregnancy were approached. Women were included at diagnosis of preeclampsia or at admission for delivery (women with normotensive pregnancies). Two cognitive assessments, the Cognitive Failure Questionnaire to assess the cognitive function subjectively before inclusion in the study, and Montreal Cognitive Assessment to assess the current cognitive function objectively before discharge from the hospital after delivery, were performed. Results We included 61 women with eclampsia, 28 with preeclampsia complicated by pulmonary edema, 38 with preeclampsia without severe features, and 26 with normotensive pregnancies. There was no difference in cognitive function from early pregnancy between groups. Women with eclampsia and preeclampsia complicated by pulmonary edema scored lower on the Montreal Cognitive Assessment at time of discharge compared with women with normotensive pregnancies. The results were attenuated in pulmonary edema after adjustment for confounders. Conclusions Women with preeclampsia complicated by pulmonary edema and in particular eclampsia had impaired cognitive function after onset of disease compared with women with normotensive pregnancies. The impairment did not seem to be present before onset of disease. Women with preeclampsia without severe features did not have impaired cognitive function

Evidence of neuroinflammation and blood–brain barrier disruption in women with preeclampsia and eclampsia

CITATION: Bergman, L. et al. 2021. Evidence of neuroinflammation and blood–brain barrier disruption in women with preeclampsia and eclampsia. Cells, 10(11):3045, doi:10.3390/cells10113045.The original publication is available at https://www.mdpi.comCerebral complications in preeclampsia are leading causes of maternal mortality. Animal models suggest that an injured blood–brain barrier and neuroinflammation may be important but there is paucity of data from human studies. Therefore, we aimed to evaluate this in women with preeclampsia and eclampsia. We included women recruited to the South African Preeclampsia Obstetric Adverse Events (PROVE) biobank. Blood and cerebrospinal fluid (CSF) were collected around delivery. CSF was analyzed for neuroinflammatory markers interleukin 1β, interleukin 6, interleukin-8 and tumor necrosis factor alpha (TNF-alpha). The CSF to plasma albumin ratio was measured to assess blood–brain barrier function. Women with eclampsia (n = 4) showed increased CSF concentrations of all pro-inflammatory cytokines and TNF-alpha compared to women with normotensive pregnancies (n = 7) and also for interleukin-6 and TNF-alpha compared to women with preeclampsia (n = 4). Women with preeclampsia also showed increases in pro-inflammatory cytokines IL-6 and IL-8 but not TNF-alpha in the CSF compared to women with normotensive pregnancies. In particular, women with eclampsia but also women with preeclampsia showed an increase in the CSF to plasma albumin ratio compared to normotensive women. In conclusion, women with preeclampsia and eclampsia show evidence of neuroinflammation and an injured blood–brain barrier. These findings are seen in particular among women with eclampsia.https://www.mdpi.com/2073-4409/10/11/3045Publisher's versio