Gene-Environment Interactions During the First Thousand Days Influence Childhood Neurological Diagnosis.

Gene-environment (G x E) interactions significantly influence neurologic outcomes. The maternal-placental-fetal (MPF) triad, neonate, or child less than 2 years may first exhibit significant brain disorders. Neuroplasticity during the first 1000 days will more likely result in life-long effects given critical periods of development. Developmental origins and life-course principles help recognize changing neurologic phenotypes across ages. Dual diagnostic approaches are discussed using representative case scenarios to highlight time-dependent G x E interactions that contribute to neurologic sequelae. Horizontal analyses identify clinically relevant phenotypic form and function at different ages. Vertical analyses integrate the approach using systems-biology from genetic through multi-organ system interactions during each developmental age to understand etiopathogenesis. The process of ontogenetic adaptation results in immediate or delayed positive and negative outcomes specific to the developmental niche, expressed either as a healthy child or one with neurologic sequelae. Maternal immune activation, ischemic placental disease, and fetal inflammatory response represent prenatal disease pathways that contribute to fetal brain injuries. These processes involve G x E interactions within the MPF triad, phenotypically expressed as fetal brain malformations or destructive injuries within the MPF triad. A neonatal minority express encephalopathy, seizures, stroke, and encephalopathy of prematurity as a continuum of trimester-specific G x E interactions. This group may later present with childhood sequelae. A healthy neonatal majority present at older ages with sequelae such as developmental disorders, epilepsy, mental health diseases, tumors, and neurodegenerative disease, often during the first 1000 days. Effective preventive, rescue, and reparative neuroprotective strategies require consideration of G x E interactions interplay over time. Addressing maternal and pediatric health disparities will maximize medical equity with positive global outcomes that reduce the burden of neurologic diseases across the lifespan.

Review of pediatric migraine headaches refractory to medical management.

OBJECTIVE: The surgical treatment of migraine headache is a recent innovation that has broadened the potential patient population who may benefit from craniofacial surgical techniques to millions of affected adults. However, the population at risk in the pediatric age group has not been clearly established. The present retrospective review was performed to provide demographic information of the adolescent migraine in a major children's hospital. This information is essential before considering surgical treatment of migraine in this age group. METHODS: Five hundred eighty-eight charts of patients aged 12 to 18 years who presented to the pediatric neurology clinic with headache in 2006 were retrospectively reviewed to evaluate for the diagnosis of migraine. Data collected included headache location, frequency, duration, intensity, associated migraine symptoms, and headache precipitants, as well as the response to medical treatment. RESULTS: Two hundred ten (36%) of 588 patients had the diagnosis of migraine headache, and 51 patients (24%) were considered refractory to the medical treatment offered. In 101 of the 210 migraine patients, anatomic location of the headaches could be identified. Thirty-nine children (19%) with refractory migraines (mean age, 14.7 years [SD, 0.3 years]) reported definitive migraine triggers. CONCLUSIONS: A significant percentage of pediatric patients with migraine headache remain refractory to medical treatment. At present, there is no good treatment regimen for migraine headaches in the pediatric population. We believe that surgical treatment of migraine headaches may be a realistic option for these patients.

Pediatric epilepsy evaluations from the prenatal perspective.

Prenatal contributions to childhood epilepsy include malformations and acquired injuries, which can occur from conception and throughout gestation. Five case histories from the Pediatric Epilepsy Service are discussed that exemplify maternal, fetal, and placental conditions that contribute to childhood epilepsy. Two full-term neonates presented with neonatal seizures, with or without accompanying encephalopathy. Placental pathology suggested antepartum maternal-placental diseases that caused or contributed to their brain disorders. Two children presented as preterm infants with systemic organ system diseases that also implicated brain injury. One child had a complicated maternal history with both genetic and acquired illnesses. Two children required epilepsy surgery, with improved seizure control despite persistent neurocognitive and neurobehavioral deficits related to diffuse encephalopathies. Dual pathology should include prenatal contributions to childhood epilepsy on both a genetic and acquired basis. Epileptologists should consider an ontogenetic approach to study the epileptic condition from a fetal neurology perspective.

Fetal and neonatal neurologic case histories: assessment of brain disorders in the context of fetal-maternal-placental disease. Part 1: Fetal neurologic consultations in the context of antepartum events and prenatal brain development.

The pediatric neurologist can contribute to a fetal diagnostic service that includes the maternal-fetal specialist as well as placental and pediatric pathologists, neonatologists, neurosurgeons, geneticists, and other pediatric subspecialists. Selected case histories of patients who presented to our fetal neurology service illustrate the wide spectrum of disease entities that are highly dependent on the time during gestation, location of brain injury, and the direct as well as indirect effects of fetal/maternal/placental disease processes on brain maturation. The pediatric neurologist has the opportunity to provide an important consultative role, bridging prenatal to neonatal life and integrating medical and ethical concerns for the child in the context of the family.