Trend in ventricle size during pregnancy and its use for prediction of ventriculoperitoneal shunt in fetal open neural tube defect.

OBJECTIVES: Fetal surgery for repair of open neural tube defect (ONTD) typically results in decreased need for a ventriculoperitoneal shunt (VPS). Our objectives were to determine the trend in ventricle size (VS) during pregnancy and whether VS and change in VS, as assessed by ultrasound, were predictive of the need for VPS in pregnancy with ONTD. METHODS: This was a retrospective analysis of prospectively collected data of consecutive pregnancies with ONTD, evaluated in a single center from January 2012 to May 2018. Two groups were identified: the first consisted of pregnancies that underwent in-utero repair (IUR) and the second those that had postnatal repair (PNR). Penalized B splines were used to determine the trend in VS, across 2-week gestational-age (GA) epochs, between 24 and 36 weeks of gestation. VS at each GA epoch and the change in VS between each GA epoch were compared between the IUR and PNR groups. To determine whether VS at any GA was predictive of VPS, receiver-operating-characteristics (ROC) curves were used and the optimal cut-off at each GA epoch was identified. Univariate analysis and multiple logistic regression were used for further analysis. RESULTS: ONTD was diagnosed in 110 fetuses, of whom 69 underwent IUR and 41 had PNR. Fetuses in the IUR group were more likely to have Chiari II malformation (100.0% vs 82.9%; P < 0.01), lower GA at delivery (34.9 ± 3.2 vs 37.1 ± 2.1 weeks; P < 0.01) and lower rates of VPS within the first year postpartum (36.2% vs 61.0%; P = 0.02) compared with the PNR group. In both groups, VS increased steadily with GA from the initial evaluation to delivery. In the IUR group, there was a significant change in VS between the 24 + 0 to 25 + 6-week and the 26 + 0 to 27 + 6-week epochs (2.3 (95% CI, 0.4-4.1) mm; P = 0.02). There was a positive trend in the change in VS at later GAs, but this was not significant. Although there was no significant change in VS in the PNR group before 30 weeks, there was a positive trend after that time. On multivariate analysis, each week of advancing GA was associated with a mean increase of 0.74 mm in VS (P < 0.0001) in both groups. VS was not associated with the level or type of lesion, but presence of Chiari II malformation was associated with a mean increase of 5.88 mm (P < 0.0001) in VS in both the IUR and PNR groups. VS was modestly predictive of need for VPS in both groups, with area under ROC curves between 0.68 and 0.76 at the different GA epochs. Change in VS between the first and last measurements was also modestly predictive of the need for VPS, with better performance in the PNR group. CONCLUSIONS: VS increased with advancing GA in all fetuses with ONTD, although in the IUR group this increase occurred immediately after fetal surgery and in the PNR group it occurred after 30 weeks of gestation. In-utero surgery was associated with a decreased rate of VPS and was more predictive of need for VPS than was VS. Postnatal factors resulting in increased need for VPS in the PNR group need to be assessed further. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.

Review: The past, present and future challenges in epilepsy-related and sudden deaths and biobanking.

Awareness and research on epilepsy-related deaths (ERD), in particular Sudden Unexpected Death in Epilepsy (SUDEP), have exponentially increased over the last two decades. Most publications have focused on guidelines that inform clinicians dealing with these deaths, educating patients, potential risk factors and mechanisms. There is a relative paucity of information available for pathologists who conduct these autopsies regarding appropriate post mortem practice and investigations. As we move from recognizing SUDEP as the most common form of ERD toward in-depth investigations into its causes and prevention, health professionals involved with these autopsies and post mortem procedure must remain fully informed. Systematizing a more comprehensive and consistent practice of examining these cases will facilitate (i) more precise determination of cause of death, (ii) identification of SUDEP for improved epidemiological surveillance (the first step for an intervention study), and (iii) biobanking and cell-based research. This article reviews how pathologists and healthcare professionals have approached ERD, current practices, logistical problems and areas to improve and harmonize. The main neuropathology, cardiac and genetic findings in SUDEP are outlined, providing a framework for best practices, integration of clinical, pathological and molecular genetic investigations in SUDEP, and ultimately prevention.

Embryonic substantia nigra grafts show directional outgrowth to cografted striatal grafts and potential for pathway reconstruction in nonhuman primate.

Transplantation of embryonic dopamine (DA) neurons has been tested as a therapy for Parkinson's disease. Most studies placed DA neurons into the striatum instead of the substantia nigra (SN). Reconstruction of this DA pathway could serve to establish a more favorable environment for control of DA release by grafted neurons. To test this we used cografts of striatum to stimulate growth of DA axons from embryonic SN that was implanted adjacent to the host SN in African green monkeys. Embryonic striatum was implanted at one of three progressive distances rostral to the SN. Immunohistochemical analysis revealed DA neuron survival and neuritic outgrowth from the SN grafts at 12-36 weeks after grafting. Each animal showed survival of substantial numbers of DA neurons. Most fibers that exited SN grafts coursed rostrally. Striatal grafts showed evidence of target-directed outgrowth and contained dense patterns of DA axons that could be traced from their origin in the SN grafts. A polarity existed for DA neurites that exited the grafts; that is, those seen caudal to the grafts did not appear to be organized into a directional outflow while those on the rostral side were arranged in linear profiles coursing toward the striatal grafts. Some TH fibers that reached the striatal grafts appeared to arise from the residual DA neurons of the SN. These findings suggest that grafted DA neurons can extend neurites toward a desired target over several millimeters through the brain stem and caudal diencephalon of the monkey brain, which favors the prospect of circuit reconstruction from grafted neurons placed into appropriate locations in their neural circuitry. Further study will assess the degree to which this approach can be used to restore motor balance in the nonhuman primate following neural transplantation.

Tissue distribution of synthetic heme analogues: studies with tin, chromium, and zinc mesoporphyrins.

The uptake in tissue of Sn-mesoporphyrin (SnMP), Cr-mesoporphyrin (CrMP) and Zn-mesoporphyrin (ZnMP) administered at doses ranging from 1 to 10 mu mol/kg BW and the effects of these compounds on heme oxygenase activity were examined in both adult and neonatal rats. SnMP and CrMP, but not ZnMP, were rapidly cleared from blood and taken up by liver, spleen and kidney where marked inhibition of heme oxygenase activity was demonstrated. None of the metalloporphyrins were detectable in brain, and no inhibition of heme oxygenase activity was demonstrable in this tissue after administration of the compounds to both adult and neonatal rats. These results demonstrate that SnMP, CrMP and ZnMP do not cross the blood brain barrier, a fact of interest in relation to the potential use of these compounds clinically.