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.

The Utility of Simulation-Based Training in Teaching Frontline Providers Modified Sarnat Encephalopathy Examination: A Randomized Controlled Pilot Trial.

Background: Limited training in targeted neurological examination makes it challenging for frontline providers to identify newborns with perinatal asphyxia eligible for therapeutic hypothermia. This training is important in the era of telemedicine, where the experts can remotely guide further care of these newborns.

Methods: This randomized controlled pilot study was conducted in a South Indian tertiary hospital.

Early role for a Na,K-ATPase () in brain development.

Osmotic equilibrium and membrane potential in animal cells depend on concentration gradients of sodium (Na) and potassium (K) ions across the plasma membrane, a function catalyzed by the Na,K-ATPase α-subunit. Here, we describe variants encoding dysfunctional α3-subunits in children affected by polymicrogyria, a developmental malformation of the cerebral cortex characterized by abnormal folding and laminar organization. To gain cell-biological insights into the spatiotemporal dynamics of prenatal expression, we built an transcriptional atlas of fetal cortical development using mRNA in situ hybridization and transcriptomic profiling of ∼125,000 individual cells with single-cell RNA sequencing (Drop-seq) from 11 areas of the midgestational human neocortex.

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.

Keratan sulfate proteoglycan as an axonal insulating barrier in the forebrain of fetuses with alobar/semi-lobar holoprosencephaly.

Background: Keratan sulfate (KS) is an abundant proteoglycan in the developing human CNS where it functions as an extracellular axonal guidance molecule, repelling glutamatergic while facilitating GABAergic axons. It ensheaths axonal fascicles. In fetal brain maturation, KS acts as a barrier to axonal penetration.

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.

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.

mTOR Inhibitors as a New Therapeutic Strategy in Treatment Resistant Epilepsy in Hemimegalencephaly: A Case Report.

Hemimegalencephaly is a hamartomatous malformation of one hemisphere. Functional hemispherectomy, the definitive treatment, is associated with significant morbidity and mortality in early infancy. Dysregulation of the mTOR pathway can result in malformations of cortical development, and mTOR inhibitors can effectively reduce seizures in tuberous sclerosis complex.

Synaptic plexi of U-fibre layer beneath focal cortical dysplasias: Role in epileptic networks.

Aims: The purpose is to demonstrate heterotopic neurones and their synaptic plexi within the U-fibre layer beneath focal cortical dysplasias (FCD).

Materials And Methods: This prospective qualitative neuropathological study included 23 patients, ages from 3 months to 17 years: resections at epileptogenic foci in 10 FCD Ia; 6 FCD IIa,b; 2 FCD IIIa,d; 3 HME; 2 TSC; 8 controls.

Techniques: immunoreactivities for synaptophysin, NeuN, MAP2, SMI32, calretinin, GFAP, vimentin, α-B-crystallin.

Olfactory Development, Part 1: Function, From Fetal Perception to Adult Wine-Tasting.

Discrimination of odorous molecules in amniotic fluid occur after 30 weeks' gestation; fetuses exhibit differential responses to maternal diet. Olfactory reflexes enable reliable neonatal testing. Olfactory bulbs can be demonstrated reliably by MRI after 30 weeks' gestation, and their hypoplasia or aplasia also documented by late prenatal and postnatal MRI.

Olfactory Development, Part 2: Neuroanatomic Maturation and Dysgeneses.

Olfactory axons project from nasal epithelium to the primitive telencephalon before olfactory bulbs form. Olfactory bulb neurons do not differentiate in situ but arrive via the rostral migratory stream. Synaptic glomeruli and concentric laminar architecture are unlike other cortices.

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.

Telencephalic Flexure and Malformations of the Lateral Cerebral (Sylvian) Fissure.

After sagittal division of the prosencephalon at 4.5 weeks of gestation, the early fetal cerebral hemisphere bends or rotates posteroventrally from seven weeks of gestation. The posterior pole of the telencephalon thus becomes not the occipital but the temporal lobe as the telencephalic flexure forms the operculum and finally the lateral cerebral or Sylvian fissure.

Synaptogenesis and Myelination in the Nucleus/Tractus Solitarius: Potential Role in Apnea of Prematurity, Congenital Central Hypoventilation, and Sudden Infant Death Syndrome.

Fetuses as early as 15 weeks' gestation exhibit rhythmical respiratory movements shown by real-time ultrasonography. The nucleus/tractus solitarius is the principal brainstem respiratory center; other medullary nuclei also participate. The purpose was to determine temporal maturation of synaptogenesis.

Phenotype/genotype correlations in epidermal nevus syndrome as a neurocristopathy.

Epidermal nevus syndrome (ENS) is a term that encompasses several phenotypes defined by the association of an epidermal nevus with one or more congenital systemic anomalies, mainly ocular, osseous and cerebral. The two most frequent, keratinocytic nevus syndrome and linear sebaceous nevus syndrome, also correspond to the neurological phenotypes. They both exhibit overlapping and distinctive features but same etiology: post-zygotic mosaic mutations in RAS genes.

Timing in neural maturation: arrest, delay, precociousness, and temporal determination of malformations.

Timing is primordial in initiating and synchronizing each developmental process in tissue morphogenesis. Maturational arrest, delay, and precociousness all are conducive to neurological dysfunction and may determine different malformations depending on when in development the faulty timing occurred, regardless of the identification of a specific genetic mutation or an epigenetic teratogenic event. Delay and arrest are distinguished by whether further progressive development over time can be expected or the condition is static.

Infantile tauopathies: Hemimegalencephaly; tuberous sclerosis complex; focal cortical dysplasia 2; ganglioglioma.

Tau is a normal microtubule-associated protein; mutations to phosphorylated or acetylated forms are neurotoxic. In many dementias of adult life tauopathies cause neuronal degeneration. Four developmental disorders of the fetal and infant brain are presented, each of which exhibits up-regulation of tau.

Morphogenesis timing of genetically programmed brain malformations in relation to epilepsy.

Cerebral malformations are best understood as abnormal tissue morphogenesis in the context of disorders of ontogenesis. In neuroembryology, the timing of onset and duration of abnormal genetic expression and neurodevelopmental processes are primordial and must always be assessed, regardless whether the dysgenesis is primarily genetic in origin or acquired in utero due to ischemia, fetal infarcts that interrupt cellular migration or exposure to teratogenic drugs or neurotoxins. Defective timing interferes with the synchrony between different developmental processes, such as synaptogenesis in relation to other aspects of neuronal maturation.

Precocious synapses in 13.5-week fetal holoprosencephalic cortex and cyclopean retina.

Background: Genetic programming of cerebral development involves tissue morphogenesis and also timing of developmental processes. Precocious synaptogenesis in the neocortical plate was previously demonstrated in 5 of 6 fetuses of 20-31 weeks gestation.

Materials And Methods: Neuropathological examination was performed of a 13-week-5-day fetus with trisomy-13, a lobar holoprosencephaly, hydrocephalus, cyclopia and absence of ears.

Synaptogenesis in the foetal and neonatal cerebellar system. 2. Pontine nuclei and cerebellar cortex.

Precise temporal and spatial sequences of synaptogenesis were demonstrated in 172 human foetuses and neonates post-mortem in transverse paraffin sections of pons and cerebellar vermis and hemispheres, using synaptophysin immunoreactivity of this protein of synaptic vesicular walls. The pontine nuclei exhibit a transitory patchy pattern not predicted from the uniform histology and reminiscent of the corpus striatum; synaptic vesicle reactivity appears at 20 weeks and is uniform by 34 weeks. In the cerebellar cortex, the vermis matures sooner than the cerebellar hemispheres and the paravermal portions earlier than the lateral folia.

Sequence of synaptogenesis in the fetal and neonatal cerebellar system - part 1: Guillain-Mollaret triangle (dentato-rubro-olivo-cerebellar circuit).

Precise temporal and spatial sequences of synaptogenesis occur in the cerebellar system, as in other synaptic circuits of the brain. In postmortem brain sections of 172 human fetuses and neonates, synaptophysin immunoreactivity was studied in nuclei of the Guillain-Mollaret triangle: dentato-olivo-rubro-cerebellar circuit. Synaptophysin demonstrates not only progressive increase in synaptic vesicles in each structure, but also shows the development of shape from amorphous globular neuronal aggregates to undulated nuclei.