Neuroembryonic and fetal brain development: Relevance to fetal/neonatal neurological training.

Insight into neuroembryology, developmental neuroanatomy and neurophysiology distinguish the diagnostic approaches of paediatric from adult neurologists and general paediatricians. These fundamental disciplines of basic neuroscience could be more effectively taught during paediatric neurology and most residency programmes, that will strengthen career-long learning. Interdisciplinary training of fetal-neonatal neurology within these programs requires working knowledge of neuroembryology applied to maternal reproductive health influencing the maternal-placental-fetal triad, neonate, and young child.

Metabolomics to Understand Alterations Induced by Physical Activity during Pregnancy.

Physical activity (PA) and exercise have been associated with a reduced risk of cancer, obesity, and diabetes. In the context of pregnancy, maintaining an active lifestyle has been shown to decrease gestational weight gain (GWG) and lower the risk of gestational diabetes mellitus (GDM), hypertension, and macrosomia in offspring. The main pathways activated by PA include BCAAs, lipids, and bile acid metabolism, thereby improving insulin resistance in pregnant individuals.

Maturation of metastases in peripheral neuroblastic tumors (neuroblastoma) of children.

Peripheral neuroblastic tumors of childhood exhibit 3 principal neural crest lineages: primitive neuroblastoma, ganglioneuroblastoma, and ganglioneuroma. They are unique in undergoing maturation of neurons (ganglion cells) and Schwann cells, thereby recapitulating normal fetal neuronal development in the brain. Precision in estimating neurogenesis is enhanced by immunoreactivities of markers of neuronal maturation.

Updated clinical recommendations for the management of tuberous sclerosis complex associated epilepsy.

Children with tuberous sclerosis complex (TSC), may experience a variety of seizure types in the first year of life, most often focal seizure sand epileptic spasms. Drug resistance is seen early in many patients, and the management of TSC associated epilepsy remain a major challenge for clinicians. In 2018 clinical recommendations for the management of TSC associated epilepsy were published by a panel of European experts.

Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial: a protocol for a multicentre, stepped-wedge cluster randomized trial.

Background: Evidence-based Practice for Improving Quality (EPIQ) is a collaborative quality improvement method adopted by the Canadian Neonatal Network that led to decreased mortality and morbidity in very preterm neonates. The Alberta Collaborative Quality Improvement Strategies to Improve Outcomes of Moderate and Late Preterm Infants (ABC-QI) Trial aims to evaluate the impact of EPIQ collaborative quality improvement strategies in moderate and late preterm neonates in Alberta, Canada.

Methods: In a 4-year, multicentre, stepped-wedge cluster randomized trial involving 12 neonatal intensive care units (NICUs), we will collect baseline data with the current practices in the first year (all NICUs in the control arm).

Sequences of synaptogenesis in the human fetal and neonatal brain by synaptophysin immunocytochemistry.

Synaptogenesis is the final phase of axonal pathfinding. Its sequences of spatial and temporal development in the immature nervous system are precisely timed and consistent. Synaptophysin, a principal structural glycoprotein of synaptic vesicle membranes regardless of the chemical transmitter substance within, is a reliable means of demonstrating sequences of synaptogenesis in human fetal brain tissue at autopsy and is resistant to postmortem autolysis.

Fetal anomaly diagnosis and termination of pregnancy.

The aim of this review was to discuss bioethics in prenatal diagnosis and health care after recent legislative and judicial changes affecting reproductive rights, such as the repeal of 'Roe v. Wade' in the United States. We recognize that abortion involves particular moralities that are not universal or shared by all cultures, groups, and individuals.

Comparison of Two Automated Targeted Metabolomics Programs to Manual Profiling by an Experienced Spectroscopist for H-NMR Spectra.

Automated programs that carry out targeted metabolite identification and quantification using proton nuclear magnetic resonance spectra can overcome time and cost barriers that limit metabolomics use. However, their performance needs to be comparable to that of an experienced spectroscopist. A previously analyzed pediatric sepsis data set of serum samples was used to compare results generated by the automated programs rDolphin and BATMAN with the results obtained by manual profiling for 58 identified metabolites.

Transitory and Vestigial Structures of the Developing Human Nervous System.

As with many body organs, the human central nervous system contains many structures and cavities that may have had functions in embryonic and fetal life but are vestigial or atrophic at maturity. Examples are the septum pellucidum, remnants of the lamina terminalis, Cajal-Retzius neurons, induseum griseum, habenula, and accessory olfactory bulb. Other structures are transitory in fetal or early postnatal life, disappearing from the mature brain.

Excitatory/Inhibitory Synaptic Ratios in Polymicrogyria and Down Syndrome Help Explain Epileptogenesis in Malformations.

Background: The ratio between excitatory (glutamatergic) and inhibitory (GABAergic) inputs into maturing individual cortical neurons influences their epileptic potential. Structural factors during development that alter synaptic inputs can be demonstrated neuropathologically. Increased mitochondrial activity identifies neurons with excessive discharge rates.

Resilience and Vulnerability: Neurodevelopment of Very Preterm Children at Four Years of Age.

Children born very preterm (VPT) are at high-risk for altered brain development and impaired neurodevelopmental outcomes but are not well-studied before school-age. We investigated 64 four-year-olds: 37 VPT children [<32 weeks gestational age [GA]; 22 males; mean GA: 28.8 weeks ± 1.

Survey on Olfactory Testing by Pediatric Neurologists: Is the Olfactory a "True" Cranial Nerve?

Background: The olfactory nerve was conceptualized in the 4th century BC by Alcmaeon and described anatomically by Winslow in 1733. Cranial nerves (CNs) were named and numbered by Soemmerring in 1791. Notions still prevail that the olfactory (CN1) is not a "true" cranial nerve.

Development of the human olfactory system.

This chapter focuses on the development of the human olfactory system. In this system, function does not require full neuroanatomical maturity. Thus, discrimination of odorous molecules, including a number within the mother's diet, occurs in amniotic fluid after 28-30 weeks of gestation, at which time the olfactory bulbs are identifiable by MRI.

New insights into a spectrum of developmental malformations related to mTOR dysregulations: challenges and perspectives.

In recent years the role of the mammalian target of rapamycin (mTOR) pathway has emerged as crucial for normal cortical development. Therefore, it is not surprising that aberrant activation of mTOR is associated with developmental malformations and epileptogenesis. A broad spectrum of malformations of cortical development, such as focal cortical dysplasia (FCD) and tuberous sclerosis complex (TSC), have been linked to either germline or somatic mutations in mTOR pathway-related genes, commonly summarised under the umbrella term 'mTORopathies'.

Area Postrema: Fetal Maturation, Tumors, Vomiting Center, Growth, Role in Neuromyelitis Optica.

Introduction: The area postrema in the caudal fourth ventricular floor is highly vascular without blood-brain or blood-cerebrospinal fluid barrier. In addition to its function as vomiting center, several others are part of the circumventricular organs for vasomotor/angiotensin II regulation, role in neuromyelitis optica related to aquaporin-4, and somatic growth and appetite regulation. Functions are immature at birth.

A Membrane Potential- and Calpain-Dependent Reversal of Caspase-1 Inhibition Regulates Canonical NLRP3 Inflammasome.

The NLRP3 inflammasome senses a range of cellular disturbances, although no consensus exists regarding a common mechanism. Canonical NLRP3 activation is blocked by high extracellular K, regardless of the activating signal. We report here that canonical NLRP3 activation leads to Ca flux and increased calpain activity.

Cerebellar networks and neuropathology of cerebellar developmental disorders.

The cerebellar system is a series of axonal projections and synaptic circuits as networks, similar to those of the limbic system and those subserving the propagation and spread of seizures. Three principal cerebellar networks are identified and cerebellar disease often affects components of the networks other than just the cerebellar cortex. Contemporary developmental neuropathology of the cerebellum is best considered in the context of alterations of developmental processes: embryonic segmentation and genetic gradients along the three axes of the neural tube, individual neuronal and glial cell differentiation, migration, synaptogenesis, and myelination.

Academic productivity after retirement in pediatric neurology and neuropathology.

Many academic neurologists and neuropathologists who retire at the peak of their careers continue to be productive in research and teaching, enhanced by years of experience and mature perspective. The early 20th-century model of institutions depending upon the generosity of such individuals to donate their time and efforts without proper recognition or compensation, despite the service, prestige, and recognition they bring to their institutions, should be reconsidered in the early 21st century in the context of fairness, honesty, dignity, and increased longevity. University pensions do not distinguish retirees who continue to contribute from those who stop working.

The 2016 Bernard Sachs Lecture: Timing in Morphogenesis and Genetic Gradients During Normal Development and in Malformations of the Nervous System.

Nervous system development is quadradimensional. Both normal ontogenesis and developmental malformations are explained in the context of the fourth dimension, timing. Timing of the onset of either the genetic expression of a mutation or an epigenetic event that may be teratogenic is primordial in determining morphogenesis and the forms of malformations with their functional consequences.

Novel Inflammatory Neuropathology in Immature Brain: (1) Fetal Tuberous Sclerosis, (2) Febrile Seizures, (3) α-B-crystallin, and (4) Role of Astrocytes.

Though the term "inflammation" is traditionally defined as proliferation or infiltration of lymphatic cells of the lymphatic immune system and macrophages or as immunoreactive proteins including cytokines, interleukins and major histocompatibility complexes, recently recognized reactions to tissue injury also are inflammation, often occurring in the central nervous system in conditions where they previously were not anticipated and where they may play a role in both pathogenesis and repair. We highlight 4 such novel inflammatory conditions revealed by neuropathologic studies: (1) inflammatory markers and cells in the brain of human fetuses with tuberous sclerosis complex and perhaps other disorders of the mechanistic target of rapamycin genetic or metabolic pathway, (2) inflammatory markers in the brain related to febrile seizures of infancy and early childhood, (3) heat-shock protein upregulation in glial cells and neurons at sites of chronic epileptic foci, and (4) the emerging role of astrocytes in the presence of and participation in inflammation. Novel evidence shows that cerebral inflammation plays a role in some genetic diseases as early as midgestation and thus is not always acquired postnatally or in adult life.

Might the olfactory bulb be an origin of olfactory auras in focal epilepsy?

Olfactory auras (phantosmia) are an infrequent phenomenon in complex focal seizures generated in the mesial temporal lobe. It is generally assumed that all such auras arise from epileptic foci in the entorhinal cortex, amygdala or rostral insula, all of which have major afferent projections from the olfactory bulb or mainly from its relay, the anterior olfactory nucleus. The histological morphology, synaptic circuitry, and foetal development of the olfactory bulb are unique.