ObjectiveMost neurodegenerative diseases contain hyperphosphorylated Tau [p-Tau]. We examined for the first time epitopes at which Tau is hyperphosphorylated in Parkinson’s disease, dementia with Lewy bodies and Alzheimer’s disease, and also select Tau kinases.MethodsPostmortem frontal cortex from Parkinson’s disease, dementia with Lewy bodies, Alzheimer’s disease and striata from Parkinson’s disease, were analyzed by immunoblots using commercially available antibodies against 20 different phospho-epitopes of Tau. Major Tau kinases were also screened. Results in diseased tissues were compared to nondiseased controls.ResultsIn Alzheimer’s disease, Tau was hyperphosphorylated at all the 20 epitopes of p-Tau. In dementia with Lewy bodies, p-Tau formation occurred at 6 sites sharing 30% overlap with Alzheimer’s disease, while in Parkinson’s frontal cortex, an area which does not degenerate, Tau hyperphosphorylation was seen at just 3 epitopes, indicating 15% overlap with Alzheimer’s disease. In Parkinson’s disease striatum, an area which undergoes considerable neurodegeneration, Tau was hyperphosphorylated at 10 epitopes, sharing 50% overlap with Alzheimer’s disease. Between frontal cortex of Parkinson’s disease and dementia with Lewy bodies, there were only two p-Tau epitopes in common. In striata of Parkinson’s disease, there were 3 clusters of Tau hyperphosphorylated at 3 contiguous sites, while two such clusters were detected in dementia with Lewy bodies; such clusters disrupt axonal transport of mitochondria, cause microtubule remodeling and result in cell death. p-GSK-3β, a major Tau kinase, was activated in all brain regions examined, except in dementia with Lewy bodies. Activation of other Tau kinases was seen in all brain regions, with no clear pattern of activation.InterpretationOur studies suggest that the three neurodegenerative diseases each have a signature-specific profile of p-Tau formation which may be useful in understanding the genesis of the diseases and for the development of a panel of specific biomarkers.

ObjectiveCompare neurodevelopment after levetiracetam (LEV) and phenobarbital (PB) for neonatal seizures.Study designRetrospective study of infants who received antiepileptic drugs (AEDs) for neonatal seizures. Effect of cumulative exposure to LEV and PB on outcomes of death, cerebral palsy (CP), and Bayley Scales of Infant Development (BSID) scores were evaluated at 24 months corrected age. Analyses were adjusted for number of electrographic seizures and gestational age.ResultsIn 280 infants with comparable seizure etiology and cranial imaging results, increased exposure to PB was associated with worse BSID cognitive and motor scores (8.1- and 9-point decrease per 100 mg/kg; p=0.01). The effect was less with LEV (2.2- and 2.6-point decrease per 300 mg/kg LEV (p=0.01). CP probability increased by 2.3-fold per 100 mg/kg PB and was not associated with increasing LEV.ConclusionIncreased exposure to PB is associated with worse neurodevelopmental outcomes than LEV. Prospective studies of outcomes of neonatal exposure to AEDs are essential.

This case series describes changes in size, vascularity, and cul-de-sac fluid in 30 patients with ectopic pregnancies who were treated with systemic methotrexate. Pretreatment and posttreatment transvaginal sonography of the ectopic pregnancies was performed with color Doppler imaging, and the images were assessed for changes in size, vascularity, and cul-de-sac free fluid. There was a trend for nonresponders to show increased vascularity on serial examinations, although this finding was also seen in a single responder. There was also a trend for nonresponders with increased vascularity to be associated with a greater increase in β-human chorionic gonadotropin levels and responders with decreased vascularity to be associated with a greater decrease in β-human chorionic gonadotropin levels.

Objectives: To assess if Doppler ultrasound improves the diagnostic accuracy of histologically confirmed RPOC. Examination of inter observer variability in diagnosis and measurement of RPOC. Methods: Retrospective analysis of and image review from ultrasound database of diagnoses of incomplete miscarriage in a tertiary referral early pregnancy unit from January to December 2014. Histological concordance was sought for those undergoing surgical management. Scan images were reviewed by two independent sonographers for accuracy of measurements and vascularity, including correct Doppler settings. Reviewers were blinded to the histological report. Results: A scan diagnosis of incomplete miscarriage was made in 699 cases of whom 117 underwent surgical management. A second procedure and repeat scan was required in 4 patients. 121 scans were reviewed. Histology confirmed RPOC in 115/121 (95%). Reviewer A disagreed with 45/121 (37%) and reviewer B 17/121 (14%) of measurements. In 8/121 (7%) of the same cases both reviewers disagreed with the original measurements. Measurements were overestimated. Power or colour Doppler was used in 96/121 (79%) cases. Reviewer A agreed with the operator's assessment of vascularity in 92/96 (96%) and reviewer B in 64/96 (66%) of scans. Vascular uptake subsequently assessed to be in the myometrium was the most common reason for disagreement. The original report concluded 15/96 (15%) of cases were avascular. Histology confirmed trophoblast in 13/15 (96%) of these. Conclusions:The diagnosis of RPOC remains subjective leading to unnecessary follow up and increased intervention rates with associated social disruption and management related complications for the patient. This dataset is being expanded to review images of all incomplete miscarriages, operation findings and histological measurements. Objectives: To assess the transvaginal sonography (TVS) findings of systemically treated ectopic pregnancies and to correlate these findings to changes in βhCG and clinical response. Methods: A retrospective analysis was performed of 30 women with ectopic pregnancies treated with systemic methotrexate (MTX) with pre-and post-treatment TVS. Patients were considered responsive to treatment if βhCG levels decreased by 15% of baseline 4-7 days following a single dose MTX. Patients were considered non-responsive if βhCG levels increased, or if a second dose of MTX or surgical intervention was required. Pre-and post-treatment images were evaluated for changes in ectopic size (increase defined as greater than 15% volume increase), vascularity and cul-de-sac fluid. OC19.04 Sonography of responsive versus non-responsive ectopic pregnanciesResults: Of the 7 responders and 23 non-responders, ectopic size increased in 57% of responders and 61% of non-responders. There was an increase in vascularity in 14% of responders compared to 39% of non-responders and a decrease in vascularity in 43% of responders compared to 35% of non-responders. Of the non-responders, increased vascularity was associated with a greater a...

INTRODUCTION: Two types of cell free DNA (cfDNA) platforms are available to screen for fetal chromosome abnormalities. The “limited” platform screens for a fixed number of chromosomal abnormalities while the “expanded” platform screens for abnormalities throughout the entire genome. We sought to compare the accuracy of these two platforms. METHODS: We performed a retrospective review of pregnancies undergoing cfDNA, invasive genetic testing, or both, between 2015-2016. Singleton high risk pregnancies were included. Maternal and newborn charts were reviewed to determine which cfDNA platform was performed and whether prenatal or postnatal genetic testing was performed. Appropriate statistical tests were performed for parametric and non-parametric data. Significant chromosome abnormalities were defined as whole chromosome aneuploidy, subchromosomal abnormalities >7 megabases and 22q deletion. RESULTS: 790 cfDNA assays were performed: 384 limited, 406 expanded. 44 chromosomal abnormalities were found (34 prenatally, 10 postnatally). 75% were common trisomies or sex chromosome aneuploidies while 25% were uncommon chromosomal abnormalities (deletions, duplications, unbalanced translocations, triploidy, rare autosomal trisomy). The expanded platform could potentially have detected 94% of the total number of abnormalities while the limited platform could potentially have detected only 75% (p=.03). CONCLUSION: We found that that 25% of chromosomal abnormalities in a high risk population cannot be detected by a limited cfDNA platform. Clinicians should consider usage of an expanded genome wide cfDNA platform that screens for pathogenic, clinically relevant, actionable chromosome abnormalities in patients who prefer non-invasive screening as first line testing.